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Cay M Kielty - One of the best experts on this subject based on the ideXlab platform.

  • platelet derived Growth Factor receptor α is a key determinant of smooth muscle α actin filaments in bone marrow derived mesenchymal stem cells
    The International Journal of Biochemistry & Cell Biology, 2007
    Co-Authors: Stephen Ball, Adrian C Shuttleworth, Cay M Kielty
    Abstract:

    Smooth muscle alpha-actin filaments are a defining feature of mesenchymal stem cells, and of mesenchyme-derived contractile smooth muscle cells, pericytes and myofibroblasts. Here, we show that adult bone marrow-derived mesenchymal stem cells express abundant cell surface Platelet-Derived Growth Factor receptor-alpha, having a high ratio to Platelet-Derived Growth Factor receptor-beta. Signaling through Platelet-Derived Growth Factor receptor-alpha increases smooth muscle alpha-actin filaments by activating RhoA, which results in Rho-associated kinase (ROCK)-dependent cofilin phosphorylation, enhancing smooth muscle alpha-actin filament polymerization, and also upregulates smooth muscle alpha-actin expression. In contrast, Platelet-Derived Growth Factor receptor-beta signaling strongly upregulates RhoE, which inhibits ROCK activity, promoting smooth muscle alpha-actin filament depolymerization. This study thus provides new insights into the distinct roles of Platelet-Derived Growth Factor receptor-alpha and -beta signaling in regulating the adult mesenchymal stem cell contractile cytoskeleton.

Andrius Kazlauskas - One of the best experts on this subject based on the ideXlab platform.

  • vascular endothelial Growth Factor acts primarily via platelet derived Growth Factor receptor α to promote proliferative vitreoretinopathy
    American Journal of Pathology, 2014
    Co-Authors: Andrius Kazlauskas, Steven Pennock, Luis J Haddock, Shizuo Mukai
    Abstract:

    Proliferative vitreoretinopathy (PVR) is a nonneovascular blinding disease and the leading cause for failure in surgical repair of rhegmatogenous retinal detachments. Once formed, PVR is difficult to treat. Hence, there is an acute interest in developing approaches to prevent PVR. Of the many Growth Factors and cytokines that accumulate in vitreous as PVR develops, neutralizing vascular endothelial Growth Factor (VEGF) A has recently been found to prevent PVR in at least one animal model. The goal of this study was to test if Food and Drug Administration–approved agents could protect the eye from PVR in multiple animal models and to further investigate the underlying mechanisms. Neutralizing VEGF with aflibercept (VEGF Trap-Eye) safely and effectively protected rabbits from PVR in multiple models of disease. Furthermore, aflibercept reduced the bioactivity of both experimental and clinical PVR vitreous. Finally, although VEGF could promote some PVR-associated cellular responses via VEGF receptors expressed on the retinal pigment epithelial cells that drive this disease, VEGF's major contribution to vitreal bioactivity occurred via Platelet-Derived Growth Factor receptor α. Thus, VEGF promotes PVR by a noncanonical ability to engage Platelet-Derived Growth Factor receptor α. These findings indicate that VEGF contributes to nonangiogenic diseases and that anti–VEGF-based therapies may be effective on a wider spectrum of diseases than previously appreciated.

  • pathological signaling via platelet derived Growth Factor receptor involves chronic activation of akt and suppression of p53
    Molecular and Cellular Biology, 2011
    Co-Authors: Hetian Lei, Gisela Velez, Andrius Kazlauskas
    Abstract:

    In contrast to direct activation of Platelet-Derived Growth Factor (PDGF) receptor α (PDGFRα) via PDGF, indirect activation via Growth Factors outside the PDGF family failed to induce dimerization, internalization, and degradation of PDGFRα. Chronically activated, monomeric PDGFRα induced prolonged activation of Akt and suppressed the level of p53. These events were sufficient to promote both cellular responses (proliferation, survival, and contraction) that are intrinsic to proliferative vitreoretinopathy (PVR) and induce the disease itself. This signature signaling pathway appeared to extend beyond PVR since deregulating PDGFRα in ways that promote solid tumors also resulted in chronic activation of Akt and a decline in the level of p53.

  • platelet derived Growth Factor plays a key role in proliferative vitreoretinopathy
    Investigative Ophthalmology & Visual Science, 1999
    Co-Authors: Anthony Andrews, Michelle D Tallquist, Philippe Soriano, Egle Balciunaite, Fee Lai Leong, Miguel F Refojo, Andrius Kazlauskas
    Abstract:

    PURPOSE The action of Growth Factors is thought to make a substantial contribution to the events leading to proliferative vitreoretinopathy (PVR). In this study, the importance of Platelet-Derived Growth Factor (PDGF) was tested in a rabbit model of PVR. METHODS The approach was to compare the extent of PVR induced by cells that do or do not express the receptors for PDGF and therefore differ in their ability to respond to PDGF. RESULTS Mouse embryo fibroblasts derived from PDGF receptor knock-out embryos that do not express either of the two PDGF receptors induced PVR poorly when injected into the eyes of rabbits that had previously undergone gas vitrectomy. Re-expression of the PDGF beta receptor in these cells did not improve the ability of the cells to cause PVR. In contrast, injection of cells expressing the PDGF alpha receptor resulted in stage 3 or higher PVR in 8 of 10 animals. CONCLUSIONS These findings show that PDGF makes an important contribution to the development of PVR in this animal model. Furthermore, there is a marked difference between the two receptors for PDGF, and it is the PDGF alpha receptor that is capable of driving events that lead to PVR.

  • regulation of chemotaxis by the platelet derived Growth Factor receptor beta
    Nature, 1994
    Co-Authors: Vikas Kundra, Jaime Escobedo, Andrius Kazlauskas, Sue Goo Rhee, Lewis T Williams, Bruce R Zetter
    Abstract:

    Chemotaxis is an important component of wound healing, development, immunity and metastasis, yet the signalling pathways that mediate chemotaxis are poorly understood. Platelet-Derived Growth Factor (PDGF) acts both as a mitogen and a chemoattractant. Upon stimulation, the tyrosine kinase PDGF receptor-beta (PDGFR-beta) autophosphorylates and forms a complex that includes SII2(Src homology 2)-domain-containing proteins such as the phosphatidylinositol-specific phospholipase C-gamma, Ras-GTPase-activating protein (GAP), and phosphatidylinositol-3-OH kinase. Specific tyrosine-to-phenylalanine substitutions in the PDGFR-beta can prevent binding of one SH2-domain-containing protein without affecting binding of other receptor-associated proteins. Here we use phospholipase C-gamma and PDGFR-beta mutants to map specific tyrosines involved in both positive and negative regulation of chemotaxis towards the PDGF-BB homodimer. Our results indicate that a delicate balance of migration-promoting (phospholipase C-gamma and phosphatidylinositol-3-OH kinase) and migration-suppressing (GAP) activities are recruited by the PDGFR-beta to drive chemotaxis towards PDGF-BB.

Hong, Mendeley Y Data) - One of the best experts on this subject based on the ideXlab platform.

  • Tumor Endothelial Marker 1 (TEM1/endosialin/CD248) Enhances Wound Healing by Interacting with Platelet-Derived Growth Factor Receptors
    2019
    Co-Authors: Hong, Mendeley Y Data)
    Abstract:

    The file includes the conclusion of the entitled paper '' Tumor Endothelial Marker 1 (TEM1/endosialin/CD248) Enhances Wound Healing by Interacting with Platelet-Derived Growth Factor Receptors.'' The abstract is below. Tumor endothelial marker 1 (TEM1), also known as endosialin or CD248, is a type I transmembrane glycoprotein containing a C-type lectin-like domain. It is highly expressed in pericytes and fibroblasts. Dermal fibroblasts play a pivotal role during cutaneous wound healing, especially in the proliferative phase. However, the physiological function of TEM1 in wound healing is still undetermined. During the process of wound healing, both TEM1 and Platelet-Derived Growth Factor (PDGF) receptor α (PDGFRα) expressions were highly up-regulated in myofibroblasts. In vivo, fibroblast activation and collagen deposition in granulation tissues were attenuated, and wound healing was retarded in TEM1-deleted mice. In vitro, the migration, adhesion, and proliferation of NIH3T3 cells were suppressed following TEM1 knockdown by short hairpin RNA. In PDGF-BB-treated NIH3T3 cells, the downstream signal, mitogenic, and chemoattractive effects were inhibited by TEM1 knockdown. Additionally, TEM1 and PDGFRα were co-localized in sub-cellular organelles in fibroblasts and the association of TEM1 and PDGFRα was demonstrated by co-immunoprecipitation. In summary, these finding suggested that TEM1, in combination with PDGFRα, plays a critical role in wound healing by enhancing the mitogenic and chemoattractive effects of PDGF-BB and collagen deposition in myofibroblasts

  • Tumor Endothelial Marker 1 (TEM1/endosialin/CD248) Enhances Wound Healing by Interacting with Platelet-Derived Growth Factor Receptors
    2019
    Co-Authors: Hong, Mendeley Y Data)
    Abstract:

    The file includes the conclusion of the entitled paper '' Tumor Endothelial Marker 1 (TEM1/endosialin/CD248) Enhances Wound Healing by Interacting with Platelet-Derived Growth Factor Receptors.'' The abstract is below. Tumor endothelial marker 1 (TEM1), also known as endosialin or CD248, is a type I transmembrane glycoprotein containing a C-type lectin-like domain. It is highly expressed in pericytes and fibroblasts. Dermal fibroblasts play a pivotal role during cutaneous wound healing, especially in the proliferative phase. However, the physiological function of TEM1 in wound healing is still undetermined. During the process of wound healing, both TEM1 and Platelet-Derived Growth Factor (PDGF) receptor α (PDGFRα) expressions were highly up-regulated in myofibroblasts. In vivo, fibroblast activation and collagen deposition in granulation tissues were attenuated, and wound healing was retarded in TEM1-deleted mice. In vitro, the migration, adhesion, and proliferation of NIH3T3 cells were suppressed following TEM1 knockdown by short hairpin RNA. In PDGF-BB-treated NIH3T3 cells, the downstream signal, mitogenic, and chemoattractive effects were inhibited by TEM1 knockdown. Additionally, TEM1 and PDGFRα were co-localized in sub-cellular organelles in fibroblasts and the association of TEM1 and PDGFRα was demonstrated by co-immunoprecipitation. In summary, these finding suggested that TEM1, in combination with PDGFRα, plays a critical role in wound healing by enhancing the mitogenic and chemoattractive effects of PDGF-BB and collagen deposition in myofibroblasts. If there are any questions, you can contact with me (jack810325@gmail.com)

Shuang Chen - One of the best experts on this subject based on the ideXlab platform.

  • itraconazole induces regression of infantile hemangioma via downregulation of the platelet derived Growth Factor d pi3k akt mtor pathway
    Journal of Investigative Dermatology, 2019
    Co-Authors: Chan Mu, Kaiwen Zhuang, Xiaoxi Xu, Shuang Chen, Bin Zheng
    Abstract:

    Infantile hemangioma is the most common benign vascular tumor of infancy. We have previously reported that itraconazole, a common antifungal agent, can clinically improve or cure infantile hemangioma; however, the underlying molecular mechanisms are still unclear. Here, we show that itraconazole treatment significantly inhibits proliferation and promotes apoptosis of the endothelial cells of mouse hemangioma cell line and infantile primary hemangioma endothelial cell. Itraconazole also remarkably reduced angiogenesis of hemangioma endothelial cell in vitro. We further performed transcriptome profiling via mRNA microarrays in hemangioma endothelial cell upon itraconazole treatment, and identified cytokine–cytokine receptor interaction as the top significantly enriched pathway. Importantly, itraconazole significantly reduced Platelet-Derived Growth Factor–D level, resulting in suppression of Platelet-Derived Growth Factor–β activation and inhibition of its downstream effectors, such as PI3K, Akt, 4E-BP1, and p70S6K, which are important for cellular Growth and survival of infantile hemangioma. In conclusion, our results suggest that Platelet-Derived Growth Factor–D is a target of itraconazole in infantile hemangioma.

Christopher C Schmidt - One of the best experts on this subject based on the ideXlab platform.

  • the effects of platelet derived Growth Factor bb on healing of the rabbit medial collateral ligament an in vivo study
    American Journal of Sports Medicine, 1998
    Co-Authors: Kevin A Hildebrand, Savio L C Woo, David W Smith, Christina R Allen, Masataka Deie, Brian J Taylor, Christopher C Schmidt
    Abstract:

    We report a biologic approach to improve medial collateral ligament healing using Growth Factors normally expressed in healing tissue. Our previous in vitro work demonstrated that Platelet-Derived Growth Factor-BB and transforming Growth Factor-beta 1 promoted fibroblast proliferation and matrix synthesis, respectively. There-fore, these Growth Factors were used in vivo to determine whether they could improve medial collateral ligament healing, whether this effect was dose-dependent, and if combinations of Growth Factors could improve healing more than individual Growth Factors. Thirty-seven rabbits had various doses of Growth Factors applied to the ruptured right medial collateral ligaments using a fibrin sealant delivery vehicle. The five groups consisted of 1) two groups receiving two doses of Platelet-Derived Growth Factor-BB, 2) two groups receiving two doses of this Growth Factor plus transforming Growth Factor-beta 1, and 3) one group receiving fibrin sealant only. After sacrifice at 6 weeks, biomechanical and histologic evaluations of the healing ligament were performed. Femur-medial collateral ligament-tibia complexes of the knees given the higher dose of Platelet-Derived Growth Factor-BB had ultimate load, energy absorbed to failure, and ultimate elongation values that were 1.6, 2.4, and 1.6 times greater than the same complexes of the control group. Adding transforming Growth Factor-beta 1 did not lead to any further increase in the structural properties of the complex compared with treatment with Platelet-Derived Growth Factor-BB. These encouraging results suggest that use of Platelet-Derived Growth Factor-BB may improve the quality of the healing medial collateral ligament, and that it may also have a similar potential for promoting healing of other ligaments.