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

Angiotensin II (Ang II) is considered to play a role in the development of glomerulosclerosis, which is characterized by excessive accumulation of mes angial matrix after mesangial cell proliferation. We have reported that pla telet-derived growth factor (PDGF) and fibroblast growth factor-2 (FGF-2) s timulate type IV collagen production by cultured human mesangial cells (HMC ). Although Ang II is well known to have a mitogenic effect in various kind s of cells, its role in the production of extracellular matrix is still und etermined. 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. Cult ured 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 t ype IV collagen, fibronectin, laminin and transforming growth factor-beta. PDGF and FGF-2 enhanced type IV production, although they did not stimulate the production of fibronectin and laminin. Ang II further increased the st imulating 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 t ype I receptor antagonist (Losartan). These data imply that Ang II is a pot ent stimulator of type IV collagen production by HMC in the presence of gro wth factors.