The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
Tohru Tateshita - One of the best experts on this subject based on the ideXlab platform.
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Effects of collagen matrix containing transforming growth factor (TGF)-β1 on Wound Contraction
Journal of Dermatological Science, 2001Co-Authors: Tohru Tateshita, Fumio KanekoAbstract:We evaluated the effectiveness of transforming growth factor (TGF)-β1 on Wound Contraction, both alone and in combination with collagen matrix, using an in vivo delayed Wound healing type model. To clarify the mechanisms involved in the effectiveness of TGF-β1, we also used a fibroblast-populated collagen gel Contraction in vitro model. Although we found that TGF-β1 significantly accelerated Contraction of the fibroblast-populated collagen gel in vitro, we demonstrated that both collagen matrix alone and 1.0 μg of TGF-β1 alone significantly inhibited Wound Contraction in the in vivo model. In addition, the combination of TGF-β1 and collagen matrix was much more effective than TGF-β1 alone, a finding which was supported by histopathological examination. Wounds treated with collagen matrix containing TGF-β1 showed horizontal rearrangement of collagen fibers in the dermal part as well as evidence of active fibroblast proliferation, which was not observed in the scar regions of controls. These results show that the application of TGF-β1 treated collagen matrix is effective for preventing Contraction producing so called ‘neodermis’ in treating a delayed healing type model and may be highly beneficial for treating chronic Wounds.
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Effects of a collagen matrix containing prostaglandin E1 on Wound Contraction
Journal of Dermatological Science, 2001Co-Authors: Li-jun Zhou, Tohru TateshitaAbstract:Abstract In this study, we evaluated the effectiveness of prostaglandin (PG) E1 in inhibiting Wound Contraction, both alone and in combination with collagen matrix, using a in vivo full thickness skin defect model. To clarify the mechanisms involved in this inhibition we also used a fibroblast-populated collagen gel Contraction in vitro model. We demonstrated that collagen matrix alone significantly inhibited Wound Contraction PG E1 alone did not. Interestingly, their combination was much more effective than either collagen matrix or PG E1 alone, a finding which was also supported by histopathological examination. Wounds treated with collagen matrix, but not control Wounds, showed horizontal rearrangement of collagen fibers in the dermal part as well as evidence of active fibroblast proliferation which was not observed in scar regions surrounded by normal dermis. With the fibroblast-populated collagen gel Contraction in vitro model, we found that PG E1 significantly inhibited Contraction at a high dose. It was concluded that collagen matrix combined with PG E1 is effective for preventing contracture producing so called neodermis than collagen matrix alone, which remains one of the most challenging problems in treating full thickness type Wounds.
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Effect of a collagen matrix containing epidermal growth factor on Wound Contraction
Wound Repair and Regeneration, 1998Co-Authors: Masayuki Inoue, Tohru Tateshita, Yoshimitsu Kuroyanagi, Nobuyuki ShioyaAbstract:: Excessive Wound Contraction is known to lead to pathological Wound contracture. Using a rabbit model, we applied a bovine type I collagen matrix sponge as a dermal substitute and human epidermal growth factor to full-thickness excisional Wounds. Wound Contraction was assessed 14 and 28 days after Wounding. It was found that both collagen matrix and epidermal growth factor significantly inhibited Wound Contraction (p 0.05; 36.5 +/- 2.8%, p < 0.05; and 39.8 +/- 2.1%, p < 0.001 at 1, 10, and 100 ng/ml of epidermal growth factor, respectively). In conclusion, collagen matrix and epidermal growth factor, particularly in combination, may be useful in the prevention of Wound contracture.
H. Paul Ehrlich - One of the best experts on this subject based on the ideXlab platform.
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Collagen Organization Critical Role in Wound Contraction
Advances in wound care, 2012Co-Authors: H. Paul Ehrlich, Thomas K. HuntAbstract:Background: Open Wound closure by Wound Contraction produces a healed defect made up mostly of dermis. Generating thicker collagen fibers condenses granulation tissue, which pulls surrounding skin into the defect. The Problem: What is the mechanism for open Wound Contraction? Is it through the generation of contractile force using sustained myosin ATPase, thus causing cell Contraction or by rapid myosin ATPase that condenses collagen fibrils into fibers? Basic/Clinical Science Addressed: The mechanism for Wound Contraction is not often debated after the discovery of the myofibroblast. Myofibroblasts are the major cell phenotype in maturing granulation tissue. It is concluded, not quite accurately, that myofibroblasts are responsible for Wound Contraction. As Wound Contraction progresses, polarized light microscopy reveals birefringence patterns associated with ever-increasing thickening of collagen fibers. Collagen fibers thicken by eliminating water between fibrils. Wound Contraction requires collagen sy...
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When the Smad signaling pathway is impaired, fibroblasts advance open Wound Contraction
Experimental and molecular pathology, 2010Co-Authors: H. Paul EhrlichAbstract:In Wound healing transforming growth factor β1 (TGFβ1), utilizing the Smad signaling pathway, advances connective tissue deposition, the transformation of fibroblasts into myofibroblasts and Wound Contraction. The compound SB-505124 disrupts the Smad signaling pathway by blocking activin receptor-like kinase phosphorylation of select Smad signaling proteins. Four full thickness excisional square 2 × 2 cm Wounds were made on the rat dorsum. On day 2, the pair of Wounds on the left received 1 μM SB-505124 in gel, and the pair on the right, controls, received gel alone. Wounds were covered with nonocclusive dressings and treated redressed daily for 4 days. No differences in day 14 Wound sizes between treatment groups were found. H&E stained sections revealed increased cell density in SB-505124 treated Wounds. Polarized light microscopy showed collagen fiber bundles birefringence intensity and organization were equivalent between treatment groups. Myofibroblast populations, identified by α-smooth muscle actin staining, were the norm in controls but absent in SB-505124 treated Wounds, which was confirmed by Western blot analysis. Blocking the Smad signaling pathway diminished connective tissue deposition and generated a deficiency in myofibroblast numbers, but Wound Contraction was unimpaired. The absence of myofibroblasts may be related to the blocking of the Smad signaling pathway or it may be related to the generation of less tension in treated Wounds, related to reduce deposited connective tissue. These findings support the notion that Wound Contraction does not require the generation of myofibroblast contractile forces, but rather the organization of newly deposited collagen fiber bundles by forces related to fibroblast locomotion.
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Topical platelet-derived growth factor in patients enhances Wound closure in the absence of Wound Contraction.
Cytokines cellular & molecular therapy, 2002Co-Authors: H. Paul Ehrlich, Bruce M. FreedmanAbstract:Recombinant human platelet-derived growth factor (PDGF) is reported to promote Wound closure in problem Wounds. The mechanism of PDGF enhancement of Wound closure is not clear. Does PDGF enhance Wound Contraction, or re-epithelialization, or both? In four patients undergoing elective surgery, a full excision 5 cm(2) punch Wound was made behind each ear. The left post-articular Wound received daily PDGF in a gel and each right post-articular Wound received placebo-gel daily. The placebo-treated Wounds closed in 19.8 days, while the PDGF-treated Wounds closed significantly faster, in 15.6 days, p=0.002. At Day 20, all healed Wounds were processed for histology. PDGF-treated Wounds showed granulation tissue beneath an uninterrupted epidermis. A fine birefringence pattern, consistent with granulation tissue, was found by polarized light microscopy. The control closed-Wounds had a smaller area of granulation tissue under an intact epidermis and polarized light microscopy showed mostly normal dermis. The presence of intact dermis within the closed-Wound site is the hallmark of Wound Contraction. Topical PDGF limits the role of Wound Contraction in Wound closure. Control Wounds healed by Wound Contraction, while PDGF-treated Wounds close by re-epithelialization and filling in with scar.
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Vanadate and the absence of myofibroblasts in Wound Contraction.
Archives of surgery (Chicago Ill. : 1960), 1999Co-Authors: H. Paul Ehrlich, Kerry Keefer, Roland L. Myers, Anthony PassanitiAbstract:Hypothesis Fibroblasts, not myofibroblasts, are responsible for Wound Contraction. Only myofibroblasts express a smooth muscle actin for which vanadate blocks its expression. Wound Contraction in vanadate-treated rats will proceed normally in the absence of myofibroblasts. Design Laboratory study using rats. Methods Wound healing in rats receiving vanadate parenterally, an inhibitor of tyrosine phosphate phosphatases, was investigated. For 21 days, treated rats received drinking water containing vanadate, 0.2 mg/mL, in isotonic sodium chloride solution, and the control rats received isotonic sodium chloride solution alone. On day 7, 4 square, full-excision Wounds were made dorsally and measured, then 2 polyvinyl alcohol sponges were placed ventrally in subcutaneous pockets. Results After 2 weeks, the Wound area in the rats receiving vanadate measured 7.1±1.8 U (mean±SD), and the Wound area in the control rats measured 7.2±2.2 U. The control rats' granulation tissue (GT) had myofibroblasts, or α-smooth muscle (α-SM) actin-positive fibroblasts, whereas the vanadate-treated group's fibroblasts were devoid of α-SM actin. By Western blot analysis, GT homogenates in the vanadate-treated group contained less α-SM actin. By electron microscopy, control rats' GT showed classic myofibroblast populations, and the collagen fiber bundles were randomly organized. In contrast, the Wounds in the vanadate-treated group showed unencumbered fibroblast populations and neatly ordered, parallel collagen fiber bundles. By polarized light microscopy, the GT of the vanadate-treated group displayed orderly collagen fiber bundles. Conclusions The differentiation of fibroblasts into myofibroblasts requires the dephosphorylation of selected tyrosine phosphate residues. In the absence of myofibroblasts, the rate of rat Wound Contraction is normal, and collagen fiber bundles have a more orderly arrangement. Myofibroblasts are not required for Wound Contraction.
Fumio Kaneko - One of the best experts on this subject based on the ideXlab platform.
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Effects of collagen matrix containing transforming growth factor (TGF)-β1 on Wound Contraction
Journal of Dermatological Science, 2001Co-Authors: Tohru Tateshita, Fumio KanekoAbstract:We evaluated the effectiveness of transforming growth factor (TGF)-β1 on Wound Contraction, both alone and in combination with collagen matrix, using an in vivo delayed Wound healing type model. To clarify the mechanisms involved in the effectiveness of TGF-β1, we also used a fibroblast-populated collagen gel Contraction in vitro model. Although we found that TGF-β1 significantly accelerated Contraction of the fibroblast-populated collagen gel in vitro, we demonstrated that both collagen matrix alone and 1.0 μg of TGF-β1 alone significantly inhibited Wound Contraction in the in vivo model. In addition, the combination of TGF-β1 and collagen matrix was much more effective than TGF-β1 alone, a finding which was supported by histopathological examination. Wounds treated with collagen matrix containing TGF-β1 showed horizontal rearrangement of collagen fibers in the dermal part as well as evidence of active fibroblast proliferation, which was not observed in the scar regions of controls. These results show that the application of TGF-β1 treated collagen matrix is effective for preventing Contraction producing so called ‘neodermis’ in treating a delayed healing type model and may be highly beneficial for treating chronic Wounds.
Neil A. Bhowmick - One of the best experts on this subject based on the ideXlab platform.
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Dermal Transforming Growth Factor-β Responsiveness Mediates Wound Contraction and Epithelial Closure
The American journal of pathology, 2009Co-Authors: Magaly Martinez-ferrer, Jeffrey M Davidson, Ali-reza Afshar-sherif, Consolate Uwamariya, Benoit De Crombrugghe, Neil A. BhowmickAbstract:Stromal-epithelial interactions are important during Wound healing. Transforming growth factor-β (TGF-β) signaling at the Wound site has been implicated in re-epithelization, inflammatory infiltration, Wound Contraction, and extracellular matrix deposition and remodeling. Ultimately, TGF-β is central to dermal scarring. Because scarless embryonic Wounds are associated with the lack of dermal TGF-β signaling, we studied the role of TGF-β signaling specifically in dermal fibroblasts through the development of a novel, inducible, conditional, and fibroblastic TGF-β type II receptor knockout (Tgfbr2dermalKO) mouse model. Full thickness excisional Wounds were studied in control and Tgfbr2dermalKO back skin. The Tgfbr2dermalKO Wounds had accelerated re-epithelization and closure compared with controls, resurfacing within 4 days of healing. The loss of TGF-β signaling in the dermis resulted in reduced collagen deposition and remodeling associated with a reduced extent of Wound Contraction and elevated macrophage infiltration. Tgfbr2dermalKO and control skin had similar numbers of myofibroblastic cells, suggesting that myofibroblastic differentiation was not responsible for reduced Wound Contraction. However, several mediators of cell-matrix interaction were reduced in the Tgfbr2dermalKO fibroblasts, including α1, α2, and β1 integrins, and collagen gel Contraction was diminished. There were associated deficiencies in actin cytoskeletal organization of vasodilator-stimulated phosphoprotein-containing lamellipodia. This study indicated that paracrine and autocrine TGF-β dermal signaling mechanisms mediate macrophage recruitment, re-epithelization, and Wound Contraction.
Cheng Peng - One of the best experts on this subject based on the ideXlab platform.
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kgf 1 accelerates Wound Contraction through the tgf β1 smad signaling pathway in a double paracrine manner
Journal of Biological Chemistry, 2019Co-Authors: Yi Peng, Qiyu Tang, Cheng PengAbstract:KGF-1 plays an important role in the Wound healing process. Loss of the KGF-1 gene in diabetic mice attenuated the process of Wound Contraction, suggesting that KGF-1 contributes to Wound Contraction. However, the mechanism remains unclear. To investigate the role of KGF-1 in diabetic Wound Contraction, we established a keratinocyte-fibroblast co-culture system. Concentrations of transforming growth factor β1 (TGF-β1) in conditioned supernatant treated with KGF-1 (KGF-1 group), tk;4KGF-1-neutralizing antibody (anti-KGF-1 group), TGF-β1 (TGF-β1tk;1 group), KGF-1 and TGF-β1-neutralizing antibody (KGF-1 + anti-TGF-β1 group) were tested by ELISA. Conditioned medium was added to fibroblast-populated collagen lattice (FPCL) to investigate the effect of KGF-1 on fibroblastqj Contraction. TGF-β1, Col-I, p-Smad2, p-Smad3, and α-smooth muscle actin (α-SMA) were examined by Western blotting. A diabetic rat Wound model was utilized to evaluate Wound morphology, histology, immunohistochemistry, and protein expression in Wound tissue after treatment with KGF-1. ELISA assays revealed that the concentration of TGF-β1 in the conditioned supernatant in the KGF-1 group was significantly higher. The contractile capacity of FPCL stimulated by conditioned medium derived from the KGF-1 group was significantly elevated; however, the contractile activity of FPCL induced by KGF-1 was attenuated by TGF-β1-neutralizing antibody. The Western blot results suggest that KGF-1 is able to stimulate TGF-β1 activation with increased Col-I, p-Smad2, p-Smad3, and α-SMA expression. Diabetic Wounds treated with KGF-1 had a higher degree of Contraction with significantly higher expression of TGF-β1, Col-I, p-Smad2, p-Smad3, and α-SMA. Our findings demonstrate that KGF-1 promotes fibroblast Contraction and accelerates Wound Contraction via the TGF-β1/Smad signaling pathway in a double-paracrine manner.
