Thrombospondin-1: A Key Protein That Induces Fibrosis in Diabetic Complications

Figure 3

The progression of fibrosis caused by expression of ECM proteins after activation of TSP-1. After binding CD36, TSP-1 activates TGF-β1 to initiate cellular fibrosis by triggering two distinct pathways that increase the quantity of expressed ECM proteins. One pathway involves Smad signaling. The receptor-regulated Smad2 and Smad3 are phosphorylated, leading to fibrosis. The other pathway involves non-Smad signals, including the ERK1/2 and MAPK p38 pathways. On the other hand, TSP-1 binding CD47 activates Rho-Rho kinase- (ROCK-) myosin and PCK pathways to enhance TSP-1 expression and TGF-β1 activation, ultimately accelerating the progression of fibrosis. TSP-1: thrombospondin-1; PKC: protein kinase C; Ang II: angiotensin II; AT1: Ang II type 1; MAPK: mitogen-activated protein kinase; ROCK: Rho kinase; TGF-β1: transforming growth factor β1; and CTGF: connective tissue growth factor.