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  • Title: [Role of PDGF-A/PDGFR-α in proliferation and transdifferentiation of fibroblasts from skin lesions of patients with systemic sclerosis].
    Author: Liu T, Zhang J.
    Journal: Nan Fang Yi Ke Da Xue Xue Bao; 2012 Apr; 32(4):496-501. PubMed ID: 22543129.
    Abstract:
    OBJECTIVE: To study the role of platelet-derived growth factor A (PDGF-A)/PDGF receptor-α (PDGFR-α) signaling pathway in the proliferation and transdifferentiation of fibroblasts (FB) into myofibroblasts (MFB) in the skin lesions of patients with systemic sclerosis (SSc). METHODS: The primary FBs isolated from the skin lesions of SSc patients and normal adult skin cultured in vitro were examined for α-smooth muscle actin (α-SMA) using immunocytochemistry. The FBs were incubated with different concentrations of PDGF-AA and the changes in their proliferative activity were quantified with MTT assay. RT-PCR was used to determine the effects of transforming growth factor-β(1) (TGF-β(1)) and PDGF-AA, either alone or in combination, on the expression levels of PDGFR-α and α-SMA mRNA in the FBs. RESULTS: Although the FBs of the two groups were morphologically similar, only FBs from the skin lesion showed positive staining for α-SMA. Below the saturated concentration of PDGF, the FBs in the two groups both proliferated in a dose-dependent manner (P<0.05), but the FBs from the SSc lesions always showed a significantly higher proliferative activity (P<0.05). PDGF-AA and TGF-β(1), alone or in combination, up-regulated the expression level of PDGFR-α and α-SMA mRNA in the FBs from SSc lesions; similar results were obtained in the control FBs, except that TGF-β(1) alone did not influence PDGFR-α mRNA expression. PDGFR-α and α-SMA mRNA always showed higher expressions in FBs in SSc lesions than in the control FBs with the same treatments (P<0.05). The expression levels of PDGFR-α and α-SMA mRNA increased in the order of untreated, PDGF-AA, TGF-β(1) and PDGF-AA plus TGF-β(1) groups and showed a strong positive correlation between them (r=0.925, P<0.05). CONCLUSION: The FBs from the skin lesions of SSc patients have a distinct feature of transdifferentiation into MFB. Over-expression of PDGFR-α on the surface of FBs from SSc lesions can bind more PDGF-AA ligands to increase cell proliferation and promote transdifferentiation to MFB, and TGF-β(1) further enhances this effect .
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