Insulin-like growth factor-1 stimulates production of mesangial cell matrix components.
Diabetic nephropathy is characterized by mesangial cell proliferation and expansion of the mesangial matrix. Insulin-like growth factor-1 (IGF-1) increases in the kidney early in experimental diabetes. The effect of IGF-1 on mesangial cell proliferation and synthesis of extracellular matrix (ECM) proteins was examined to test the hypothesis that IGF-1 stimulates mesangial cells to synthesize ECM proteins. ECM proteins were measured by immunoprecipitation after metabolic labeling of rat mesangial cells in culture. IGF-1 caused a 2.4-fold increase in mesangial cell proliferation as measured by 3H-thymidine incorporation. IGF-1 caused an increase in cellular laminin, fibronectin and type IV collagen, 46.8 +/- 15.4%, 31.3 +/- 11.4%, and 27.7 +/- 12.6% increase respectively compared to control cells. IGF-1 did not effect cellular type 1 collagen, decrease of 8.2 +/- 8.7%. There was a trend toward increased total protein synthesis by IGF-1, 36.5 +/- 2.5%. In summary, IGF-1 stimulates ECM component production by mesangial cells. Thus, IGF-1 has the capacity to mediate the histologic changes characteristic of diabetic nephropathy.
Schreiber
B D
BD
Department of Medicine, University of Vermont College of Medicine, Burlington, USA.
Hughes
M L
ML
Groggel
G C
GC
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000187:drug effects*; D005353:Fibronectins / Q000096:biosynthesis / Q000187:drug effects; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007797:Laminin / Q000096:biosynthesis / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D007334:Insulin-Like Growth Factor I; D003094:Collagen