Fig. 7.

Pathways leading to collagen expression. TGF-β induces Smad3 COOH-terminal phosphorylation in an ALK5-dependent fashion. Smad3 translocates to the nucleus and mediates collagen expression in addition to increasing HIF-1α expression in an mTORC1 dependent fashion. Both Smad3 and HIF-1α are required for maximal TGF-β-induced collagen expression. A: under normoxia, mTOR1 inhibition using rapamycin prevents TGF-β-induced HIF-1α expression and reduces collagen expression. B: under hypoxia (or hypoxia mimic), HIF-1α is stabilized in a manner that is independent of mTORC1. As a result, mTORC1 inhibition does not affect TGF-β-induced collagen expression.