Endothelin stimulates PDGF secretion in cultured human mesangial cells

Abstract

Endothelin, a 17-DKa peptide originally described as a potent vasoconstrictor, also stimulates the release of important regulators of glomerular hemodynamics such as atrial natriuretic factor and renin. In the present study we investigated the role of endothelin in the release of another potent vasoconstrictor and mitogen of human mesangial cells, the platelet-derived growth factor. Endothelin stimulated PDGF release at 12 hours and the effect was sustained for 36 hours. This effect was associated with the enhanced induction of mRNAs encoding PDGF A- and B-chain. Endothelin also induced mitogenesis in human mesangial cells which was accompanied by activation of phospholipase C with increased inositol phosphate turnover. These data suggest a mechanism by which endothelin may regulate mesangial cell function in disease states.

Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing.

“…By their nature, however, culture models exclude complex interactions and, therefore, we are unable to rule out additional indirect effects of bosentan in vivo. For example, ET-1 stimulates production of PDGF in human mesangial cells (29), and the possibility that bosentan prevented such downstream events in the hepatic injury response remains open.…”

Nephroprotection of an ET A -Receptor Blocker (LU 135252) in Salt-Loaded Uninephrectomized Stroke-Prone Spontaneously Hypertensive Rats

“…7,31 Furthermore, ET-1 stimulates the production of cytokines such as platelet-derived growth factor. 30 In the rat kidney, ET A receptors have been demonstrated in mesangial cells and ET B receptors in endothelial and epithelial cells. 32 In hypertensive rats, the specific ET A receptor antagonist BQ123 reduces glomerular filtration rate by increasing arteriolar resistance.…”

“…11 Furthermore, in SHR the receptor affinity for ET-1 is increased. 28 The inhibitory effect of ET A receptor blockade on the development of glomerulosclerosis and of interstitial or vascular lesions appears plausible in view of the known renal actions of ET-1, ie, mitogenic effects on mesangial cells 29,30 and increased expression of fibronectin and collagen. 7,31 Furthermore, ET-1 stimulates the production of cytokines such as platelet-derived growth factor.…”

Regulation of rat mesangial cell growth by diadenosine phosphates.

“…Since a number of vasopressor hormones, such as angiotensin II, vasopressin and endothelin, also act as growth factors on vascular smooth muscle cells or MC (17,18), it was tested in the present study, whether also AP5A and AP6A stimulate growth of MC. Furthermore, both dinucleotides were tested for interactions with polypeptide growth factors.…”