Platelet-derived growth factor synthesis in mesangial cells: induction by multiple peptide mitogens.

Abstract

Platelet-derived growth factor (PDGF) has been implicated in several nonmalignant pathophysiological processes, including proliferative diseases of the kidney. Glomerular mesangial cells secrete a PDGF-like factor and express the PDGF A-chain and c-sis (or B-chain) mRNAs. We report here that both mRNAs are induced by serum and this effect can be mimicked by recombinant PDGF, which also markedly stimulates DNA synthesis. Other growth factors, such as epidermal growth factor (EGF), transforming growth factor type alpha, basic fibroblast growth factor (bFGF), and tumor necrosis factor type alpha (TNF-alpha) also are mitogenic for human mesangial cells and induce expression of the PDGF mRNAs. EGF, TNF-alpha, and bFGF also stimulate these cells to secrete a PDGF-like factor. Furthermore, anti-PDGF antibody partially abrogates the mitogenic effect of EGF, suggesting that mitogen-stimulated PDGF synthesis in mesangial cells is at least partly responsible for cell growth induced by other growth factors. In contrast to these results, transforming growth factor type beta (TGF-beta), while inducing both mRNAs, is not mitogenic, indicating that its effect on message levels can be dissociated from DNA synthesis. These data suggest that several peptide growth factors regulate the growth of mesangial cells and that PDGF may be an effector molecule that plays a role in the mitogenic response to many of these growth stimuli.

Inhibition of Interleukin-10 by the Immunomodulator AS101 Reduces Mesangial Cell Proliferation in Experimental Mesangioproliferative Glomerulonephritis

“…Alternatively, growth factors may modulate the expression of each other. For example the mesangial mitogenic factor EGF induces the expression of PDGF, whereas blocking PDGF with anti-PDGF antibody abrogates the mitogenic effect of EGF-induced MC proliferation (42). Similarly, Gas6 induces mesangial cell proliferation via activation of STAT3 (25) and STAT3 was recently shown to activate the IL-10 promoter in macrophages (43).…”

ECM homeostasis in renal diseases: a genomic approach

“…The complexity of the actions of cytokines is reflected by their multifunctionality, by the interaction between different cytokines, by the fact that they may have different actions in different locations in the cell, and, hypothetically, by different actions of the same cytokines in different time frames [4]. Most of the cytokines are stored and synthesized in infiltrating inflammatory cells such as activated monocytes/macrophages and lymphocytes [5], but many are also synthesized by resident renal cells [6,7]. The latent forms of transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF) are also derived from platelets [8,9].…”

Human Platelets Stimulate Mesangial Cells to Produce Monocyte Chemoattractant Protein-1 via the CD40/CD40 Ligand Pathway and May Amplify Glomerular Injury

“…Human MC were established and characterized as reported previously (26). Cells were cultured in Waymouth medium (Life Technologies, Grand Island, NY) supplemented with 17% heat-inactivated fetal bovine serum (FBS), 100 U/ml penicillin, 100 g/ml streptomy- cin, 2 mM L-glutamine, 2 mM sodium pyruvate, 1% (vol/vol) nonessential amino acids, and 26 g/ml of bovine insulin (all Life Technologies).…”