Mesangial cells express PDGF mRNAs and proliferate in response to PDGF

Abstract

Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin and is released and/or synthesized by platelets, macrophages, endothelial cells, and rat mesangial cells. In the present investigation, we found that human glomerular mesangial cells in culture release a PDGF-like protein which competes for 125I-PDGF binding to human foreskin fibroblasts and is mitogenic for these fibroblasts. The competing and to a lesser extent the mitogenic activities present in the conditioned medium are partially recognized by an anti-PDGF antibody. Northern blot analysis of poly(A)+ RNA from human mesangial cells demonstrates the expression of both PDGF A- and B-chain mRNAs. PDGF also binds to mesangial cells in a specific manner and stimulates DNA synthesis and cell proliferation. These data suggest that a PDGF-like protein secreted by mesangial cells or released from platelets, monocytes, or endothelial cells during glomerular inflammation may function as an autocrine or a paracrine growth factor for these cells. The biological role of PDGF in mediating proliferative and other inflammatory events in the glomerulus remains to be identified.

Insulin-like Growth Factor-I Induces Renal Cell Hypertrophy via a Calcineurin-dependent Mechanism

“…Rat MCs were cultured from glomeruli isolated by differential sieving as previously described (14). Epithelial cells were removed by digestion with collagenase, and glomerular cores were cultured in RPMI (Life Technologies, Inc., Gaithersburg, MD) supplemented with antibiotics and 17% fetal calf serum.…”

Cross‐talk between transmembrane signalling systems: a prerequisite for the delicate regulation of glomerular haemodynamics by mesangial cells

“…Several studies demonstrated that mesangial cells possess specific receptors for a number of vasoactive substances that couple to phospholipase C. Receptors for angiotensin I1 [45,72], vasopressin [27,73], PDGF [74] and LTD4 [75] have been identified on mesangial cells. Binding of these agents to their specific receptors is associated with activation of a phospholipase C that specifically cleaves PIP2 to yield DAG and IP3.…”

Modulatory role of platelet-derived growth factor on cytokine-induced nerve growth factor synthesis in rat glomerular mesangial cells

“…It has been shown that mouse, rat and human glomerular mesangial cells in culture release PDGF which stimulates DNA synthesis in an autocrine manner [11,16,25]. Findings that PDGF receptor expression is up-regulated in kidney rejection and that PDGF production is enhanced in active glomerulonephritis [16,[32][33][34][35] imply an important role for PDGF in immune responses in the kidney.…”

“…Findings that PDGF receptor expression is up-regulated in kidney rejection and that PDGF production is enhanced in active glomerulonephritis [16,[32][33][34][35] imply an important role for PDGF in immune responses in the kidney. Furthermore, antibodies to PDGF inhibit mesangial cell proliferation and matrix expansion seen in rats with mesangial proliferative nephritis induced by an antibody to the Thy-I antigen that is expressed on mesangial cells [36].…”

“…These cell types invade the mesangial matrix and seem to be the major local sources of cytokines and growth-modulating factors. However, the mesangial cells themselves are able to synthesize and release different cytokines and growth factors, including IL-1 (13], IL-6 [14], TNF-a [15], platelet-derived growth factor (PDGF) [16] and transforming growth factor-fl (TGF-,8) [17]. Moreover, they express functional receptors for most of these agents and proliferate in response to IL-1 [13], IL-6 [14] and PDGF [16].…”