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. 1995 Nov;147(5):1372–1382.

Autocrine growth regulation of human glomerular mesangial cells is primarily mediated by basic fibroblast growth factor.

A Francki 1, P Uciechowski 1, J Floege 1, J von der Ohe 1, K Resch 1, H H Radeke 1
PMCID: PMC1869518  PMID: 7485400

Abstract

For various forms of human glomerulonephritis a close relationship between inflammatory injury and a local mesangial proliferative response has been described. Herein, we used primary cultures of human glomerular mesangial cells (HMCs) from five different donors to determine the autocrine growth-inducing capacity of their supernatants after stimulation with different cytokines and lipopolysaccharide (LPS) to determine whether this effect is due to basic fibroblast growth factor (bFGF). The basal growth-inducing capacity of supernatants collected from serum-free cultured HMC and concentrated 100-fold above a cut-off size of 10 kd was significantly increased by interleukin (IL)-1 beta, platelet-derived growth factor (PDGF), and LPS up to 15-fold, but not by IL-1 alpha, IL-6, or bFGF. An anti-human bFGF antibody blocked the majority of IL-1 or LPS-induced proliferative effect of supernatants; complete inhibition was achieved by a combination of anti-human bFGF- and anti-human platelet-derived growth factor antibodies. HMCs express different isoforms of bFGF (18, 21.5, and 24 kd) in membrane, cytosolic, and nuclear fractions. All isoforms of bFGF were found in the nuclear fraction of HMC, whether stimulated or not. Immunoblots for bFGF protein of HMC demonstrated that only a approximate to 16 kd bFGF protein was released into HMC supernatants after stimulation with IL-1 beta, platelet-derived growth factor-BB, and LPS. The 18 kd isoform of bFGF accumulated in the membranes but was not released after stimulation with IL-1 alpha, IL-6, and bFGF, suggesting that its release was a prerequisite for autocrine growth stimulation. By means of reverse transcription polymerase chain reaction controlled by Southern blots, bFGF-mRNA expression of HMC was enhanced by IL-1 alpha, IL-1 beta, and LPS. Finally, we were able to show that HMCs are expressing bFGF receptors. In summary, our data demonstrate for the first time that the autocrine proliferative response of HMC to major inflammatory factors may primarily be mediated by bFGF.

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