Affiliation:
1. Department of Science Education, Jeju National University , Jeju , 63063 , Korea
2. Department of Biotechnology, Korea National University of Transportation , Chungbuk , 27909 , Korea
Abstract
Abstract
Hypertrophic scarring (HTS) is a common fibroproliferative disorder that typically follows thermal and other injuries involving the deep dermis. The underlying pathogenic mechanisms are regulated by transforming growth factor-β (TGF-β); however, the exact mechanisms in HTS have not been elucidated. We conducted this study to explore the cellular signaling mechanisms for expression of Sar1a, a coat protein complex II-associated small GTPase, in HTS fibroblasts (HTSF). We found that Sar1a was upregulated in HTSF as compared to that in normal fibroblasts. Furthermore, stimulation of TGF-β1 increased the expression of Sar1a in HTSF, and small interfering RNA for Sar1a suppressed procollagen-I (PC-I) secretion. Next we investigated the signaling mechanism from TGF-β1 to Sar1a expression and its association with PC-I secretion. In the presence of TGF-β-activated kinase 1 (TAK1), c-Jun N-terminal kinase, or p38 inhibitors, the effect of TGF-β1 on Sar1a expression and PC-I secretion significantly decreased; however, it had no effect on collagen-1A (Col-1A) expression. Further, the inhibitors of Smad3 or extracellular signal-regulated kinases inhibited TGF-β1-induced Col-1A expression but had no effect on PC-I secretion and Sar1a expression. Taken together, our results suggested that TGF-β1 induces Sar1a expression through TAK1 signaling and this signaling event regulates PC-I secretion in HTSF.
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