Differential effects of insulin-like growth factor I and platelet-derived growth factor on growth response, matrix formation, and cytosolic free calcium of glomerular mesangial cells of spontaneously hypertensive and normotensive rats.
In this study, we compared the cellular functions of cultured glomerular mesangial cells (MC) from spontaneously hypertensive rats (SHR) and from normotensive Wistar-Kyoto rats (WKY) in response to the growth factors insulin-like growth factor I (IGF-I) and platelet-derived growth factor (PDGF). IGF-I and PDGF at a concentration above 2 ng/ml and a combination of both tested growth factors exerted a highly elevated growth response of SHR MC versus WKY MC. The total RNA synthesis induced by IGF-I and PDGF was increased in SHR MC as compared with WKY MC, while the overall protein synthesis showed no differences between both strains. Analysis of cell-associated fibronectin accumulation and incorporation of proline into collagenous proteins revealed an enhanced basal and PDGF-stimulated matrix formation of SHR MC which was not dependent on the increased production of autocrine matrix-stimulatory mediators by SHR MC. Changes of cytosolic free calcium - [Ca2+]i - could not be correlated with the enhanced responsiveness of SHR MC to the tested growth factors. The described differences of cellular functions between SHR and WKY MC may contribute to pronounced glomerular alterations such as glomerulosclerosis seen in primary and secondary forms of hypertension.
Heidenreich
S
S
Department of Medicine, University of Mûnster, Germany.
Tepel
M
M
Lang
D
D
Rahn
K H
KH
Zidek
W
W
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005353:Fibronectins / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011392:Proline / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D010982:Platelet-Derived Growth Factor; D012313:RNA; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D011392:Proline; D002118:Calcium