Effects of epidermal growth factor on collagen expression by rat kidney mesangial cells in culture

Increased collagen production by mesangial cells Flays a key role in the de velopment and progression of glomerular sclerosis. These changes reflect in part the impact of growth factors on mesangial cells. Since mesangial cell s possess receptors for epidermal growth factor (EGF) and since previous st udies have documented that EGF affects collagen synthesis in other cell typ es, we have examined the effects of EGF on collagen biosynthesis by rat kid ney mesangial (RKM) cells in culture. Exposure for 24 h to EGF did not subs tantially affect the growth rate of RKM cells. While the types of collagen produced by RKM cells (types I, III, IV and V) were unaltered by exposure t o EGF, total collagen production was reduced (similar to 50%). This decreas e in collagen expression was not uniform for each collagen type. Type I col lagen production was inhibited by similar to 50%, both type III and type IV expression were each reduced by similar to 30%. but type V collagen produc tion was suppressed by only similar to 15%, The reduction in type I collage n synthesis was accounted for mainly by a decrease in type I homotrimer pro duction. Since type I molecules represent similar to 95% of the total colla gen produced, the decrease in overall collagen expression reflects a specif ic suppression by EGF on type I homotrimer production in mesangial cells. A s EGF exposure resulted in a decrease in collagen production, these results suggest that the increases in synthesis and deposition of collagen observe d in several glomerular diseases likely do not reflect the short-term effec ts of EGF on mesangial cells. Rather, these findings suggest the possibilit y that EGF or EGF-like growth factors may ameliorate the effects of other s oluble factors that cause enhanced matrix production and deposition in rena l diseases. (C) 2000 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved.