کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1964247 | 1058536 | 2008 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Caveolin-1 increases basal and TGF-β1-induced expression of type I procollagen through PI-3 kinase/Akt/mTOR pathway in human dermal fibroblasts Caveolin-1 increases basal and TGF-β1-induced expression of type I procollagen through PI-3 kinase/Akt/mTOR pathway in human dermal fibroblasts](/preview/png/1964247.png)
Caveolin-1 (Cav-1) is a major structural protein of caveolae and plays an important role as a negative regulator of various signaling pathways such as the transforming growth factor-β (TGF-β)/smad pathway. In this study, we investigated the role of cav-1 on basal and TGF-β1-induced expression of type I procollagen in human dermal fibroblasts. Our results demonstrated that basal and TGF-β1-induced expression of type I procollagen were significantly increased by adenoviral cav-1 (Ad-cav-1) overexpression, while the basal level of type I procollagen was decreased by cav-1 siRNA. Overexpression of cav-1 inhibited TGF-β1-induced phosphorylation of smad3 and transcription of 3TP-Lux and SBE luciferase reporters, suggesting that cav-1 may inhibit the TGF-β1/smad signaling pathway. We observed that TGF-β1-induced type I procollagen expression was decreased by smad3 siRNA transfection. However, the reduction of TGF-β1-induced type I procollagen expression by smad3 siRNA was reversed by cav-1 overexpression. In addition, our results also showed that TGF-β1 treatment increased the phosphorylation of Akt, and Ad-cav-1 infection augmented this TGF-β1-induced phosphorylation of Akt. Ad-myr-Akt infection significantly increased the basal expression of type I procollagen. In contrast, TGF-β1-induced type I procollagen expression was decreased by Akt siRNA transfection and the PI3-kinase inhibitor, LY294002, inhibited the TGF-β1-induced type I procollagen expression and also inhibited the cav-1-induced expression of type I procollagen. In conclusion, our results suggest that cav-1 increases the basal and TGF-β1-induced expression of type I procollagen by regulating two opposite signaling pathways: inhibiting TGF-β1/smad signaling and activating a PI-3 kinase/Akt/mTOR-dependent pathway in human dermal fibroblasts, ultimately resulting in increased type I procollagen expression.
Journal: Cellular Signalling - Volume 20, Issue 7, July 2008, Pages 1313–1319