Role of PDGF-A/PDGFR-α in proliferation and transdifferentiation of fibroblasts from skin lesions of patients with systemic sclerosis.
- Author:
Tong LIU
1
;
Jing ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Actins; metabolism; Adult; Cell Proliferation; Cell Transdifferentiation; Cells, Cultured; Female; Fibroblasts; cytology; Humans; Male; Middle Aged; Myofibroblasts; cytology; Platelet-Derived Growth Factor; metabolism; Receptor, Platelet-Derived Growth Factor alpha; metabolism; Scleroderma, Systemic; metabolism; pathology; Signal Transduction; Transforming Growth Factor beta; pharmacology
- From: Journal of Southern Medical University 2012;32(4):496-501
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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).
METHODSThe 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.
RESULTSAlthough 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).
CONCLUSIONThe 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 .
