Angiotensin II further enhances type IV collagen production stimulated by platelet‐derived growth factor and fibroblast growth factor‐2 in cultured human mesangial cells

SUMMARY: Angiotensin II (Ang II) is considered to play a role in the development of glomerulosclerosis, which is characterized by excessive accumulation of mesangial matrix after mesangial cell proliferation. We have reported that platelet‐derived growth factor (PDGF) and fibroblast growth factor‐2 (FGF‐2) stimulate type IV collagen production by cultured human mesangial cells (HMC). Although Ang II is well known to have a mitogenic effect in various kinds of cells, its role in the production of extracellular matrix is still undetermined. This study was designed to examine the effect of Ang II and its interaction with PDGF and FGF‐2 in type IV collagen production by HMC. Cultured HMC were incubated with Ang II with or without PDGF or FGF‐2 for 72 h and type IV collagen, fibronectin and laminin in the cell supernatants were measured. Ang II (10−6–10−8) itself did not change the production of type IV collagen, fibronectin, laminin and transforming growth factor‐β. PDGF and FGF‐2 enhanced type IV production, although they did not stimulate the production of fibronectin and laminin. Ang II further increased the stimulating effect of PDGF and FGF‐2 in type IV collagen production in a dose‐dependent manner. This effect of Ang II was completely blocked by Ang II type I receptor antagonist (Losartan). These data imply that Ang II is a potent stimulator of type IV collagen production by HMC in the presence of growth factors.