The Experts below are selected from a list of 3465 Experts worldwide ranked by ideXlab platform
Barbara Gawronska-kozak - One of the best experts on this subject based on the ideXlab platform.
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FOXN1 Control of Skin Function
Applied Sciences, 2020Co-Authors: Barbara Gawronska-kozakAbstract:The forkhead box N1 (FOXN1) transcription factor regulates biological processes of the thymus and skin. Loss-of-function mutations in FOXN1 cause the nude phenotype in humans, mice, and rats, which is characterized by hairless skin and a lack of thymus. This review focuses on the role of FOXN1 in skin biology, including epidermal, dermal, and dermal white adipose tissue (dWAT) skin components. In particular, the role of FOXN1 in the scar-forming skin wound healing process is discussed, underscoring that FOXN1 inactivity in nude mice is permissive for scar-less cutaneous wound resolution.
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Impairment of the Hif-1α regulatory pathway in FOXN1-deficient (FOXN1-/-) mice affects the skin wound healing process
2020Co-Authors: Sylwia Machcinska, Marta Kopcewicz, Katarzyna Walendzik, Joanna Bukowska, Barbara Gawronska-kozakAbstract:ABSTRACT Hypoxia and hypoxia-regulated factors [e. g., hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1), thioredoxin-1 (Trx-1), aryl hydrocarbon receptor nuclear translocator 2 (Arnt-2)] have essential roles in skin wound healing. Using FOXN1−/− mice that can heal skin injuries in a unique scarless manner, we investigated the interaction between FOXN1 and hypoxia-regulated factors. The FOXN1−/− mice displayed impairments in the regulation of Hif-1α, Trx-1 and Fih-1 but not Arnt-2 during the healing process. An analysis of wounded skin showed that the skin of the FOXN1−/− mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in transforming growth factor β (Tgfβ-3) and collagen III expression. An in vitro analysis revealed that FOXN1 overexpression in keratinocytes isolated from the skin of the FOXN1−/− mice led to reduced Hif-1α expression in normoxic but not hypoxic cultures and inhibited Fih-1 expression exclusively under hypoxic conditions. These data indicate that in the skin, FOXN1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, FOXN1 is a limiting factor for Hif-1α.
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The Transcription Factor FOXN1 Regulates Skin Adipogenesis and Affects Susceptibility to Diet-Induced Obesity.
The Journal of investigative dermatology, 2019Co-Authors: Katarzyna Walendzik, Marta Kopcewicz, Joanna Bukowska, Grzegorz Panasiewicz, Bozena Szafranska, Barbara Gawronska-kozakAbstract:FOXN1, a transcription factor expressed in the epidermis, regulates keratinocyte differentiation and participates in skin wound healing. In this study, we explored the impact of FOXN1 insufficiency on diet-stimulated weight gain and dermal white adipose tissue regulation in the intact and wounded skin of FOXN1eGFP/+ (heterozygotes, FOXN1-insufficient) mice in the context of age and diet. The results showed that on a high-fat diet, FOXN1eGFP/+ mice gained significantly less body weight than their FOXN1+/+ counterparts (FOXN1-sufficient mice). The intact and wounded skin of FOXN1eGFP/+ mice displayed abrogated expression of the master regulators of adipogenesis, PPARγ, FABP4, and leptin, which decreased with age in FOXN1+/+ mice. FOXN1 insufficiency also resulted in a decreased percentage of adipocyte-committed precursor cells (CD24+) in the skin. The proadipogenic pathway genes Bmp2, Igf2, and Mest showed a gradual decrease in expression that accompanied the gradual inactivation of FOXN1 in the skin of FOXN1+/+, FOXN1eGFP/+, and FOXN1eGFP/eGFP (lack of FOXN1) mice. Bone morphogenetic protein 2 and insulin-like growth factor 2 signals colocalized with FOXN1-eGFP in the epidermis and in hair follicles. These data demonstrated that FOXN1 initiates the cascade of adipogenic signaling that regulates skin homeostasis and wound healing and affects susceptibility to diet-induced obesity.
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Wnt signaling and the transcription factor FOXN1 contribute to cutaneous wound repair in mice.
Connective tissue research, 2019Co-Authors: Joanna Bukowska, Marta Kopcewicz, Katarzyna Walendzik, Patrycja Cierniak, Barbara Gawronska-kozakAbstract:Aim: The transcription factor FOXN1 is a regulator of scar-ended cutaneous wound healing in mice. However, the link between FOXN1 and Wnt signaling has not been explored in the context of cutaneous...
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FOXN1 in Skin Development, Homeostasis and Wound Healing
International journal of molecular sciences, 2018Co-Authors: Joanna Bukowska, Marta Kopcewicz, Katarzyna Walendzik, Barbara Gawronska-kozakAbstract:Intensive research effort has focused on cellular and molecular mechanisms that regulate skin biology, including the phenomenon of scar-free skin healing during foetal life. Transcription factors are the key molecules that tune gene expression and either promote or suppress gene transcription. The epidermis is the source of transcription factors that regulate many functions of epidermal cells such as proliferation, differentiation, apoptosis, and migration. Furthermore, the activation of epidermal transcription factors also causes changes in the dermal compartment of the skin. This review focuses on the transcription factor FOXN1 and its role in skin biology. The regulatory function of FOXN1 in the skin relates to physiological (development and homeostasis) and pathological (skin wound healing) conditions. In particular, the pivotal role of FOXN1 in skin development and the acquisition of the adult skin phenotype, which coincides with losing the ability of scar-free healing, is discussed. Thus, genetic manipulations with FOXN1 expression, specifically those introducing conditional FOXN1 silencing in a FOXN1+/+ organism or its knock-in in a FOXN1−/− model, may provide future perspectives for regenerative medicine.
Marta Kopcewicz - One of the best experts on this subject based on the ideXlab platform.
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Impairment of the Hif-1α regulatory pathway in FOXN1-deficient (FOXN1-/-) mice affects the skin wound healing process
2020Co-Authors: Sylwia Machcinska, Marta Kopcewicz, Katarzyna Walendzik, Joanna Bukowska, Barbara Gawronska-kozakAbstract:ABSTRACT Hypoxia and hypoxia-regulated factors [e. g., hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1), thioredoxin-1 (Trx-1), aryl hydrocarbon receptor nuclear translocator 2 (Arnt-2)] have essential roles in skin wound healing. Using FOXN1−/− mice that can heal skin injuries in a unique scarless manner, we investigated the interaction between FOXN1 and hypoxia-regulated factors. The FOXN1−/− mice displayed impairments in the regulation of Hif-1α, Trx-1 and Fih-1 but not Arnt-2 during the healing process. An analysis of wounded skin showed that the skin of the FOXN1−/− mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in transforming growth factor β (Tgfβ-3) and collagen III expression. An in vitro analysis revealed that FOXN1 overexpression in keratinocytes isolated from the skin of the FOXN1−/− mice led to reduced Hif-1α expression in normoxic but not hypoxic cultures and inhibited Fih-1 expression exclusively under hypoxic conditions. These data indicate that in the skin, FOXN1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, FOXN1 is a limiting factor for Hif-1α.
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impairment of the hif 1α regulatory pathway in FOXN1 deficient FOXN1 mice affects the skin wound healing process
bioRxiv, 2020Co-Authors: Sylwia Machcinska, Katarzyna Walendzik, Marta Kopcewicz, Joanna Bukowska, Barbara GawronskakozakAbstract:ABSTRACT Hypoxia and hypoxia-regulated factors [e. g., hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1), thioredoxin-1 (Trx-1), aryl hydrocarbon receptor nuclear translocator 2 (Arnt-2)] have essential roles in skin wound healing. Using FOXN1−/− mice that can heal skin injuries in a unique scarless manner, we investigated the interaction between FOXN1 and hypoxia-regulated factors. The FOXN1−/− mice displayed impairments in the regulation of Hif-1α, Trx-1 and Fih-1 but not Arnt-2 during the healing process. An analysis of wounded skin showed that the skin of the FOXN1−/− mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in transforming growth factor β (Tgfβ-3) and collagen III expression. An in vitro analysis revealed that FOXN1 overexpression in keratinocytes isolated from the skin of the FOXN1−/− mice led to reduced Hif-1α expression in normoxic but not hypoxic cultures and inhibited Fih-1 expression exclusively under hypoxic conditions. These data indicate that in the skin, FOXN1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, FOXN1 is a limiting factor for Hif-1α.
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The Transcription Factor FOXN1 Regulates Skin Adipogenesis and Affects Susceptibility to Diet-Induced Obesity.
The Journal of investigative dermatology, 2019Co-Authors: Katarzyna Walendzik, Marta Kopcewicz, Joanna Bukowska, Grzegorz Panasiewicz, Bozena Szafranska, Barbara Gawronska-kozakAbstract:FOXN1, a transcription factor expressed in the epidermis, regulates keratinocyte differentiation and participates in skin wound healing. In this study, we explored the impact of FOXN1 insufficiency on diet-stimulated weight gain and dermal white adipose tissue regulation in the intact and wounded skin of FOXN1eGFP/+ (heterozygotes, FOXN1-insufficient) mice in the context of age and diet. The results showed that on a high-fat diet, FOXN1eGFP/+ mice gained significantly less body weight than their FOXN1+/+ counterparts (FOXN1-sufficient mice). The intact and wounded skin of FOXN1eGFP/+ mice displayed abrogated expression of the master regulators of adipogenesis, PPARγ, FABP4, and leptin, which decreased with age in FOXN1+/+ mice. FOXN1 insufficiency also resulted in a decreased percentage of adipocyte-committed precursor cells (CD24+) in the skin. The proadipogenic pathway genes Bmp2, Igf2, and Mest showed a gradual decrease in expression that accompanied the gradual inactivation of FOXN1 in the skin of FOXN1+/+, FOXN1eGFP/+, and FOXN1eGFP/eGFP (lack of FOXN1) mice. Bone morphogenetic protein 2 and insulin-like growth factor 2 signals colocalized with FOXN1-eGFP in the epidermis and in hair follicles. These data demonstrated that FOXN1 initiates the cascade of adipogenic signaling that regulates skin homeostasis and wound healing and affects susceptibility to diet-induced obesity.
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Wnt signaling and the transcription factor FOXN1 contribute to cutaneous wound repair in mice.
Connective tissue research, 2019Co-Authors: Joanna Bukowska, Marta Kopcewicz, Katarzyna Walendzik, Patrycja Cierniak, Barbara Gawronska-kozakAbstract:Aim: The transcription factor FOXN1 is a regulator of scar-ended cutaneous wound healing in mice. However, the link between FOXN1 and Wnt signaling has not been explored in the context of cutaneous...
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FOXN1 in Skin Development, Homeostasis and Wound Healing
International journal of molecular sciences, 2018Co-Authors: Joanna Bukowska, Marta Kopcewicz, Katarzyna Walendzik, Barbara Gawronska-kozakAbstract:Intensive research effort has focused on cellular and molecular mechanisms that regulate skin biology, including the phenomenon of scar-free skin healing during foetal life. Transcription factors are the key molecules that tune gene expression and either promote or suppress gene transcription. The epidermis is the source of transcription factors that regulate many functions of epidermal cells such as proliferation, differentiation, apoptosis, and migration. Furthermore, the activation of epidermal transcription factors also causes changes in the dermal compartment of the skin. This review focuses on the transcription factor FOXN1 and its role in skin biology. The regulatory function of FOXN1 in the skin relates to physiological (development and homeostasis) and pathological (skin wound healing) conditions. In particular, the pivotal role of FOXN1 in skin development and the acquisition of the adult skin phenotype, which coincides with losing the ability of scar-free healing, is discussed. Thus, genetic manipulations with FOXN1 expression, specifically those introducing conditional FOXN1 silencing in a FOXN1+/+ organism or its knock-in in a FOXN1−/− model, may provide future perspectives for regenerative medicine.
Joanna Bukowska - One of the best experts on this subject based on the ideXlab platform.
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Impairment of the Hif-1α regulatory pathway in FOXN1-deficient (FOXN1-/-) mice affects the skin wound healing process
2020Co-Authors: Sylwia Machcinska, Marta Kopcewicz, Katarzyna Walendzik, Joanna Bukowska, Barbara Gawronska-kozakAbstract:ABSTRACT Hypoxia and hypoxia-regulated factors [e. g., hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1), thioredoxin-1 (Trx-1), aryl hydrocarbon receptor nuclear translocator 2 (Arnt-2)] have essential roles in skin wound healing. Using FOXN1−/− mice that can heal skin injuries in a unique scarless manner, we investigated the interaction between FOXN1 and hypoxia-regulated factors. The FOXN1−/− mice displayed impairments in the regulation of Hif-1α, Trx-1 and Fih-1 but not Arnt-2 during the healing process. An analysis of wounded skin showed that the skin of the FOXN1−/− mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in transforming growth factor β (Tgfβ-3) and collagen III expression. An in vitro analysis revealed that FOXN1 overexpression in keratinocytes isolated from the skin of the FOXN1−/− mice led to reduced Hif-1α expression in normoxic but not hypoxic cultures and inhibited Fih-1 expression exclusively under hypoxic conditions. These data indicate that in the skin, FOXN1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, FOXN1 is a limiting factor for Hif-1α.
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impairment of the hif 1α regulatory pathway in FOXN1 deficient FOXN1 mice affects the skin wound healing process
bioRxiv, 2020Co-Authors: Sylwia Machcinska, Katarzyna Walendzik, Marta Kopcewicz, Joanna Bukowska, Barbara GawronskakozakAbstract:ABSTRACT Hypoxia and hypoxia-regulated factors [e. g., hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1), thioredoxin-1 (Trx-1), aryl hydrocarbon receptor nuclear translocator 2 (Arnt-2)] have essential roles in skin wound healing. Using FOXN1−/− mice that can heal skin injuries in a unique scarless manner, we investigated the interaction between FOXN1 and hypoxia-regulated factors. The FOXN1−/− mice displayed impairments in the regulation of Hif-1α, Trx-1 and Fih-1 but not Arnt-2 during the healing process. An analysis of wounded skin showed that the skin of the FOXN1−/− mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in transforming growth factor β (Tgfβ-3) and collagen III expression. An in vitro analysis revealed that FOXN1 overexpression in keratinocytes isolated from the skin of the FOXN1−/− mice led to reduced Hif-1α expression in normoxic but not hypoxic cultures and inhibited Fih-1 expression exclusively under hypoxic conditions. These data indicate that in the skin, FOXN1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, FOXN1 is a limiting factor for Hif-1α.
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The Transcription Factor FOXN1 Regulates Skin Adipogenesis and Affects Susceptibility to Diet-Induced Obesity.
The Journal of investigative dermatology, 2019Co-Authors: Katarzyna Walendzik, Marta Kopcewicz, Joanna Bukowska, Grzegorz Panasiewicz, Bozena Szafranska, Barbara Gawronska-kozakAbstract:FOXN1, a transcription factor expressed in the epidermis, regulates keratinocyte differentiation and participates in skin wound healing. In this study, we explored the impact of FOXN1 insufficiency on diet-stimulated weight gain and dermal white adipose tissue regulation in the intact and wounded skin of FOXN1eGFP/+ (heterozygotes, FOXN1-insufficient) mice in the context of age and diet. The results showed that on a high-fat diet, FOXN1eGFP/+ mice gained significantly less body weight than their FOXN1+/+ counterparts (FOXN1-sufficient mice). The intact and wounded skin of FOXN1eGFP/+ mice displayed abrogated expression of the master regulators of adipogenesis, PPARγ, FABP4, and leptin, which decreased with age in FOXN1+/+ mice. FOXN1 insufficiency also resulted in a decreased percentage of adipocyte-committed precursor cells (CD24+) in the skin. The proadipogenic pathway genes Bmp2, Igf2, and Mest showed a gradual decrease in expression that accompanied the gradual inactivation of FOXN1 in the skin of FOXN1+/+, FOXN1eGFP/+, and FOXN1eGFP/eGFP (lack of FOXN1) mice. Bone morphogenetic protein 2 and insulin-like growth factor 2 signals colocalized with FOXN1-eGFP in the epidermis and in hair follicles. These data demonstrated that FOXN1 initiates the cascade of adipogenic signaling that regulates skin homeostasis and wound healing and affects susceptibility to diet-induced obesity.
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Wnt signaling and the transcription factor FOXN1 contribute to cutaneous wound repair in mice.
Connective tissue research, 2019Co-Authors: Joanna Bukowska, Marta Kopcewicz, Katarzyna Walendzik, Patrycja Cierniak, Barbara Gawronska-kozakAbstract:Aim: The transcription factor FOXN1 is a regulator of scar-ended cutaneous wound healing in mice. However, the link between FOXN1 and Wnt signaling has not been explored in the context of cutaneous...
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FOXN1 in Skin Development, Homeostasis and Wound Healing
International journal of molecular sciences, 2018Co-Authors: Joanna Bukowska, Marta Kopcewicz, Katarzyna Walendzik, Barbara Gawronska-kozakAbstract:Intensive research effort has focused on cellular and molecular mechanisms that regulate skin biology, including the phenomenon of scar-free skin healing during foetal life. Transcription factors are the key molecules that tune gene expression and either promote or suppress gene transcription. The epidermis is the source of transcription factors that regulate many functions of epidermal cells such as proliferation, differentiation, apoptosis, and migration. Furthermore, the activation of epidermal transcription factors also causes changes in the dermal compartment of the skin. This review focuses on the transcription factor FOXN1 and its role in skin biology. The regulatory function of FOXN1 in the skin relates to physiological (development and homeostasis) and pathological (skin wound healing) conditions. In particular, the pivotal role of FOXN1 in skin development and the acquisition of the adult skin phenotype, which coincides with losing the ability of scar-free healing, is discussed. Thus, genetic manipulations with FOXN1 expression, specifically those introducing conditional FOXN1 silencing in a FOXN1+/+ organism or its knock-in in a FOXN1−/− model, may provide future perspectives for regenerative medicine.
Anna Kur-piotrowska - One of the best experts on this subject based on the ideXlab platform.
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FOXN1 expression in keratinocytes is stimulated by hypoxia: further evidence of its role in skin wound healing.
Scientific reports, 2018Co-Authors: Anna Kur-piotrowska, Marta Kopcewicz, Joanna Bukowska, Mariola A. Dietrich, Joanna Nynca, Mariola Słowińska, Barbara Gawronska-kozakAbstract:Recent studies have shown that the transcription factor FOXN1, which is expressed in keratinocytes, is involved in the skin wound healing process, yet how FOXN1 functions remains largely unknown. Our latest data indicate that FOXN1 drives skin healing via engagement in re-epithelization and the epithelial-mesenchymal transition (EMT) process. In the present study, 2D-DIGE proteomic profiling analysis of in vitro cultured keratinocytes transfected with adenoviral vector carrying FOXN1-GFP or GFP alone (control) revealed forty proteins with differential abundance between the compared groups. Among the proteins with FOXN1-dependent expression, several enable adaptation to hypoxia. Subsequent experiments revealed that hypoxic conditions (1% O2) stimulate endogenous and exogenous (transfected Ad-FOXN1) FOXN1 expression in cultured keratinocytes. A proteomics analysis also identified proteins that can act as a factors controlling the balance between cell proliferation, differentiation and apoptosis in response to FOXN1. We also showed that in C57BL/6 keratinocytes, the stimulation of FOXN1 by hypoxia is accompanied by increases in Mmp-9 expression. These data corroborate the detected co-localization of FOXN1 and Mmp-9 expression in vivo in post-wounding skin samples of FOXN1::Egfp transgenic mice. Together, our data indicate that FOXN1 orchestrates cellular changes in keratinocytes in both physiological (self-renewal) and pathological (skin wound healing) contexts.
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Neotenic phenomenon in gene expression in the skin of FOXN1- deficient (nude) mice - a projection for regenerative skin wound healing.
BMC genomics, 2017Co-Authors: Anna Kur-piotrowska, Marta Kopcewicz, Anna Grabowska, Leslie P. Kozak, Paweł Sachadyn, Barbara Gawronska-kozakAbstract:Mouse fetuses up to 16 day of embryonic development and nude (FOXN1- deficient) mice are examples of animals that undergo regenerative (scar-free) skin healing. The expression of transcription factor FOXN1 in the epidermis of mouse fetuses begins at embryonic day 16.5 which coincides with the transition point from scar-free to scar-forming skin wound healing. In the present study, we tested the hypothesis that FOXN1 expression in the skin is an essential condition to establish the adult skin phenotype and that FOXN1 inactivity in nude mice keeps skin in the immature stage resembling the phenomena of neoteny. Uninjured skin of adult C57BL/6J (B6) mice, mouse fetuses at days 14 (E14) and 18 (E18) of embryonic development and B6.Cg-FOXN1 nu (nude) mice were characterized for their gene expression profiles by RNA sequencing that was validated through qRT-PCR, Western Blot and immunohistochemistry. Differentially regulated genes indicated that nude mice were more similar to E14 (model of regenerative healing) and B6 were more similar to E18 (model of reparative healing). The up-regulated genes in nude and E14 mice were associated with tissue remodeling, cytoskeletal rearrangement, wound healing and immune response, whereas the down-regulated genes were associated with differentiation. E14 and nude mice exhibit prominent up-regulation of keratin (Krt23, -73, -82, -16, -17), involucrin (Ivl) and filaggrin (Flg2) genes. The transcription factors associated with the Hox genes known to specify cell fate during embryonic development and promote embryonic stem cells differentiation were down-regulated in both nude and E14. Among the genes enriched in the nude skin but not shared with E14 fetuses were members of the Wnt and matrix metalloproteinases (Mmps) families whereas Bmp and Notch related genes were down-regulated. In summary, FOXN1 appears to be a pivotal control element of the developmental program and skin maturation. Nude mice may be considered as a model of neoteny among mammals. The resemblance of gene expression profiles in the skin of both nude and E14 mice are direct or indirect consequences of the FOXN1 deficiency. FOXN1 appears to regulate the balance between cell proliferation and differentiation and its inactivity creates a pro-regenerative environment.
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FOXN1 Transcription Factor Regulates Wound Healing of Skin through Promoting Epithelial-Mesenchymal Transition.
PloS one, 2016Co-Authors: Barbara Gawronska-kozak, Anna Kur-piotrowska, Anna Grabowska, Marta KopcewiczAbstract:Transcription factors are key molecules that finely tune gene expression in response to injury. We focused on the role of a transcription factor, FOXN1, whose expression is limited to the skin and thymus epithelium. Our previous studies showed that FOXN1 inactivity in nude mice creates a pro-regenerative environment during skin wound healing. To explore the mechanistic role of FOXN1 in the skin wound healing process, we analyzed post-injured skin tissues from FOXN1::Egfp transgenic and C57BL/6 mice with Western Blotting, qRT-PCR, immunofluorescence and flow cytometric assays. FOXN1 expression in non-injured skin localized to the epidermis and hair follicles. Post-injured skin tissues showed an intense FOXN1-eGFP signal at the wound margin and in leading epithelial tongue, where it co-localized with keratin 16, a marker of activated keratinocytes. This data support the concept that suprabasal keratinocytes, expressing FOXN1, are key cells in the process of re-epithelialization. The occurrence of an epithelial-mesenchymal transition (EMT) was confirmed by high levels of Snail1 and Mmp-9 expression as well as through co-localization of vimentin/E-cadherin-positive cells in dermis tissue at four days post-wounding. Involvement of FOXN1 in the EMT process was verified by co-localization of FOXN1-eGFP cells with Snail1 in histological sections. Flow cytometric analysis showed the increase of double positive E-cadherin/N-cadherin cells within FOXN1-eGFP population of post-wounded skin cells isolates, which corroborated histological and gene expression analyses. Together, our findings indicate that FOXN1 acts as regulator of the skin wound healing process through engagement in re-epithelization and possible involvement in scar formation due to FOXN1 activity during the EMT process.
Anna Grabowska - One of the best experts on this subject based on the ideXlab platform.
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FOXN1 Transcription Factor in Epithelial Growth and Wound Healing.
Molecular and cellular biology, 2017Co-Authors: Anna Grabowska, Tomasz WilanowskiAbstract:FOXN1 is a prodifferentiation transcription factor in the skin epithelium. Recently, it has also emerged as an important player in controlling the skin wound healing process, as it actively participates in reepithelialization and is thought to be responsible for scar formation. FOXN1 positivity is also a feature of pigmented keratinocytes, including nevi, and FOXN1 is an attribute of benign epithelial tumors. The lack of FOXN1 favors the skin regeneration process displayed by nude mice, pointing to FOXN1 as a switch between regeneration and reparative processes. The stem cell niche provides a functional source of cells after the loss of tissue following wounding. The involvement of prodifferentiation factors in the regulation of this pool of stem cells is suggested. However, the exact mechanism is still under question, and we speculate that the FOXN1 transcription factor is involved in this process. This review analyzes the pleiotropic effects of FOXN1 in the skin, its function in the tumorigenesis process, and its potential role in depletion of the stem cell niche after injury, as well as its suggested mechanistic role, acting in a cell-autonomous and a non-cell-autonomous manner during skin self-renewal.
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Neotenic phenomenon in gene expression in the skin of FOXN1- deficient (nude) mice - a projection for regenerative skin wound healing.
BMC genomics, 2017Co-Authors: Anna Kur-piotrowska, Marta Kopcewicz, Anna Grabowska, Leslie P. Kozak, Paweł Sachadyn, Barbara Gawronska-kozakAbstract:Mouse fetuses up to 16 day of embryonic development and nude (FOXN1- deficient) mice are examples of animals that undergo regenerative (scar-free) skin healing. The expression of transcription factor FOXN1 in the epidermis of mouse fetuses begins at embryonic day 16.5 which coincides with the transition point from scar-free to scar-forming skin wound healing. In the present study, we tested the hypothesis that FOXN1 expression in the skin is an essential condition to establish the adult skin phenotype and that FOXN1 inactivity in nude mice keeps skin in the immature stage resembling the phenomena of neoteny. Uninjured skin of adult C57BL/6J (B6) mice, mouse fetuses at days 14 (E14) and 18 (E18) of embryonic development and B6.Cg-FOXN1 nu (nude) mice were characterized for their gene expression profiles by RNA sequencing that was validated through qRT-PCR, Western Blot and immunohistochemistry. Differentially regulated genes indicated that nude mice were more similar to E14 (model of regenerative healing) and B6 were more similar to E18 (model of reparative healing). The up-regulated genes in nude and E14 mice were associated with tissue remodeling, cytoskeletal rearrangement, wound healing and immune response, whereas the down-regulated genes were associated with differentiation. E14 and nude mice exhibit prominent up-regulation of keratin (Krt23, -73, -82, -16, -17), involucrin (Ivl) and filaggrin (Flg2) genes. The transcription factors associated with the Hox genes known to specify cell fate during embryonic development and promote embryonic stem cells differentiation were down-regulated in both nude and E14. Among the genes enriched in the nude skin but not shared with E14 fetuses were members of the Wnt and matrix metalloproteinases (Mmps) families whereas Bmp and Notch related genes were down-regulated. In summary, FOXN1 appears to be a pivotal control element of the developmental program and skin maturation. Nude mice may be considered as a model of neoteny among mammals. The resemblance of gene expression profiles in the skin of both nude and E14 mice are direct or indirect consequences of the FOXN1 deficiency. FOXN1 appears to regulate the balance between cell proliferation and differentiation and its inactivity creates a pro-regenerative environment.
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FOXN1 Transcription Factor Regulates Wound Healing of Skin through Promoting Epithelial-Mesenchymal Transition.
PloS one, 2016Co-Authors: Barbara Gawronska-kozak, Anna Kur-piotrowska, Anna Grabowska, Marta KopcewiczAbstract:Transcription factors are key molecules that finely tune gene expression in response to injury. We focused on the role of a transcription factor, FOXN1, whose expression is limited to the skin and thymus epithelium. Our previous studies showed that FOXN1 inactivity in nude mice creates a pro-regenerative environment during skin wound healing. To explore the mechanistic role of FOXN1 in the skin wound healing process, we analyzed post-injured skin tissues from FOXN1::Egfp transgenic and C57BL/6 mice with Western Blotting, qRT-PCR, immunofluorescence and flow cytometric assays. FOXN1 expression in non-injured skin localized to the epidermis and hair follicles. Post-injured skin tissues showed an intense FOXN1-eGFP signal at the wound margin and in leading epithelial tongue, where it co-localized with keratin 16, a marker of activated keratinocytes. This data support the concept that suprabasal keratinocytes, expressing FOXN1, are key cells in the process of re-epithelialization. The occurrence of an epithelial-mesenchymal transition (EMT) was confirmed by high levels of Snail1 and Mmp-9 expression as well as through co-localization of vimentin/E-cadherin-positive cells in dermis tissue at four days post-wounding. Involvement of FOXN1 in the EMT process was verified by co-localization of FOXN1-eGFP cells with Snail1 in histological sections. Flow cytometric analysis showed the increase of double positive E-cadherin/N-cadherin cells within FOXN1-eGFP population of post-wounded skin cells isolates, which corroborated histological and gene expression analyses. Together, our findings indicate that FOXN1 acts as regulator of the skin wound healing process through engagement in re-epithelization and possible involvement in scar formation due to FOXN1 activity during the EMT process.
