Mesangial cells in the pathogenesis of progressive glomerular disease in animal models.
Increasing evidence supports a role for glomerular mesangial cell proliferation and over-production of extracellular matrix by mesangial cells in the development of focal or diffuse glomerulosclerosis. Experimental data obtained mainly in the chronic progressive remnant kidney model and in the acute mesangioproliferative anti-Thy 1.1 glomerulonephritis in rats have shed some insights into the factors governing mesangial cell proliferation and matrix synthesis in vivo. In these experimental models, mesangial cell activation can be demonstrated early in the course of disease as exemplified by the de novo expression by the mesangial cell of a smooth muscle "specific" actin isotype (i.e., alpha-smooth muscle actin). Following mesangial cell activation, cellular proliferation ensues both in the acute anti-Thy 1.1 model and, to a lesser degree, in the chronic remnant kidney model. While a multitude of mitogens for mesangial cells has been proposed on the basis of in vitro experiments, the factors involved in the regulation of mesangial cell proliferation in vivo remain largely undefined. Three growth factors which may have important roles in the in vivo mesangioproliferative response are platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta). All three cytokine growth factors are present in various inflammatory cells as well as in mesangial cells themselves, thereby allowing these factors to mediate cell proliferation by either paracrine and/or autocrine pathways. In vivo studies show that PDGF, bFGF, and TGF-beta participate in the mesangial cell proliferation and/or the mesangial matrix expansion that follows mesangial cell injury with anti-Thy 1.1 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
Floege
J
J
Abteilung Nephrologie, Medizinische Hochschule Hannover.
Johnson
R J
RJ
Couser
W G
WG
D000818:Animals; D002455:Cell Division / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000473:pathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006133:Growth Substances / Q000502:physiology
D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D003094:Collagen