| Objective To study the expression of ALK1in dermal fibroblasts of scleroderma (SSc) and its role in the production of fibronectin and PAI-1.Methods The expression of Alk1was defined by Western blot and Immunofluorescence, both in normal and SSc dermal fibroblasts. A specific ALKl siRNA was designed to knockdown ALK1, and transient transfected into normal and scleroderma fibroblasts for72h, with or without TGF-β1for24h.Results Our results showed that ALK1was expressed in both human normal and SSc dermal fibroblasts. ALK1could be detected in both cellular membrane and cytoplasm.In SScfibroblasts, ALKlwas much more than in nonnal.ALK1depletion via siRNA in human normal fibroblasts inhibited expression of ALK1, fibronectin and PAI-1. TGFβ1increased the expression of ALK1, fibronectin and PAI-1, and this increase was blocked byALK1siRNA.Conlusion TGFp can increase production of fibronectin and PAI-1through ALK1.ALK1may be an important regulator in the pathogenesis of scleroderma. |
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