Modulation of Endogenous Smad Expression in Normal Skin Fibroblasts by Transforming Growth Factor-β

2000 ◽  
Vol 258 (2) ◽  
pp. 374-383 ◽  
Author(s):  
Yasuji Mori ◽  
Shu-Jen Chen ◽  
John Varga
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Normal Skin ◽  
Transforming Growth Factor Β ◽  
Skin Fibroblasts

Increased expression of the transforming growth factor β–inducible gene HIC-5 in systemic sclerosis skin and fibroblasts: a novel antifibrotic therapeutic target

Rheumatology ◽  
2020 ◽  
Vol 59 (10) ◽  
pp. 3092-3098 ◽  
Author(s):  
Sonsoles Piera-Velazquez ◽  
Jolanta Fertala ◽  
Gonzalo Huaman-Vargas ◽  
Natalia Louneva ◽  
Sergio A Jiménez
Keyword(s):  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Normal Skin ◽  
Transforming Growth Factor Β ◽  
Dermal Fibroblasts ◽  
Skin Fibroblasts ◽  
Tissue Fibrosis ◽  
Protein Levels ◽  
Antifibrotic Therapy ◽  
Tgf Β1

Abstract Objective SSc is a systemic fibrotic disease affecting skin, numerous internal organs and the microvasculature. The molecular pathogenesis of SSc tissue fibrosis has not been fully elucidated, although TGF-β1 plays a crucial role. The Hic-5 protein encoded by the TGF-β1-inducible HIC-5 gene participates in numerous TGF-β-mediated pathways, however, the role of Hic-5 in SSc fibrosis has not been investigated. The aim of this study was to examine HIC-5 involvement in SSc tissue fibrosis. Methods Affected skin from three patients with diffuse SSc and dermal fibroblasts cultured from affected and non-affected SSc skin were examined for HIC-5 and COL1A1 gene expression. Real-time PCR, IF microscopy, western blotting and small interfering RNA–mediated HIC-5 were performed. Results HIC-5 and COL1A1 transcripts and Hic-5, type 1 collagen (COL1) and α-smooth muscle actin (α-SMA) protein levels were increased in clinically affected SSc skin compared with normal skin and in cultured dermal fibroblasts from affected SSc skin compared with non-affected skin fibroblasts from the same patients. HIC-5 knockdown caused a marked reduction of COL1 production in SSc dermal fibroblasts. Conclusion HIC-5 expression is increased in affected SSc skin compared with skin from normal individuals. Affected SSc skin fibroblasts display increased HIC-5 and COL1A1 expression compared with non-affected skin fibroblasts from the same patients. Hic-5 protein was significantly increased in cultured SSc dermal fibroblasts. HIC-5 mRNA knockdown in SSc fibroblasts caused >50% reduction of COL1 production. Although these are preliminary results owing to the small number of skin samples studied, they indicate that Hic-5 plays a role in the profibrotic activation of SSc dermal fibroblasts and may represent a novel molecular target for antifibrotic therapy in SSc.

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