Elastic fiber proteins in the glomerular mesangium in vivo and in cell culture

Background. Glomerular capillaries of the mammalian kidney are exposed to h igh intraluminal hydrostatic pressures and require elastic constraint to ma intain size, shape, and integrity. previous morphological and functional st udies indicated that the extracellular matrices of glomeruli, that is, base ment membrane and mesangial matrix, contribute to glomerular resilience and mechanical stability. Immunofluorescence microscopy findings demonstrated elastic fiber components to be located in the renal vasculature. including glomeruli. The aim of this study was to clarify the exact glomerular locali zation, composition, and cellular production of these proteins. Methods. We examined the renal distribution of the elastic fiber proteins f ibrillin-1. emilin. microfibril-associated glycoproteins (MAGPs) 1 and 2, l atent transforming growth factor-binding protein-1 (LTBP-1), and elastin us ing immunohistology and immunoelectron microscopy of human, rat, and mouse kidneys. In mesangial cell cultures, we also studied the expression and ext racellular deposition of such proteins by use of Northern blotting and immu nocytochemistry. Results. Fibrillin-1, emilin. MAGPs 1 and 2. and LTBP-1 were present in glo meruli of mouse, rat, and human kidney, where they were located predominant ly in the mesangial extracellular matrix underlying glomerular endothelium and basement membrane. Several of these proteins, as well as elastin, were also expressed in the renal vasculature. While elastin localized to the glo merular vascular pole in afferent and efferent arterioles extending to Bowm an's capsule, it was not found in the glomerular capillary tuft. Cultured m esangial cells of rat, mouse, and human kidneys expressed mRNAs of fibrilli n-1, emilin, MAGP-2, and elastin, and the respective proteins localized wit hin and outside of mesangial cells, as shown by immunocytochemistry. mRNA e xpression of fibrillin-1, emilin, and elastin was strong in quiescent mesan gial cells; their gene expression was further up-regulated by transforming growth factor-pr, while it was transiently reduced when cells were exposed to mitogenic 10% fetal calf serum and platelet-derived growth factor. Conclusions. These findings demonstrate that specific elastic fiber protein s are produced and secreted by mesangial cells. This process is regulated b y growth factors; Their abundance in the extracellular matrix of the mesang ium is in keeping with the concept that elastic fiber proteins contribute t o the mechanical stability and elastic strength of the glomerular capillary tuft.