The transforming growth factor b (TGF-b) induces synthesis and
the secretion of collagen and elastin, and also inhibits the expression
of enzymes involved in the breakdown of collagens such as
MMP-1, MMP-3, and MMP-9 (Chiang et al., 2012; Rittie and
Fisher, 2002). TGF-b binds with TGF-b receptor I and phosphorylates
Smad proteins Smad2 and Smad3, which can form heteromeric
complexes with Smad4. The complex is transferred into
the nucleus of fibroblasts, resulting in collagen gene transcription.