Laboratory Investigation

Kidney International (1990) 37, 1256–1262; doi:10.1038/ki.1990.109

Prostaglandins and rat glomerular mesangial cell proliferation

Paolo Menè1 and Michael J Dunn1

1Departments of Medicine and Physiology and Biophysics, Case Western Reserve University School of Medicine, and Division of Nephrology, University Hospitals of Cleveland, Cleveland, Ohio, USA.

Correspondence: MJ Dunn MD, Department of Medicine, Division of Nephrology, University Hospitals of Cleveland, 2074 Abington Road, Cleveland, Ohio 44106, USA.

Present address: Cattedra di Nefrologia Medica, 2a Clinica Medica, Policlinico Umberto I, Viale del Policlinico, 00161 Rome, Italy.

Received 8 June 1989; Revised 18 December 1989; Accepted 18 December 1989.

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Abstract

Prostaglandins and rat mesangial cell proliferation. Arachidonate metabolites modulate glomerular mesangial cell contractility through specific receptors coupled to phospholipase C or adenylate cyclase. The resulting intracellular signals, including changes of cytosolic Ca2+, pH, and cyclic adenosine 3'5'-monophosphate (cAMP) are known to also regulate the growth of many cell types. Since eicosanoids have been shown to interfere with cell proliferation in culture, we studied DNA synthesis and cell number in rat mesangial cell cultures exposed to a selective phospholipase C activator, prostaglandin F2alpha (PGF2alpha), or to the cAMP-stimulating PGI2 analogue, Iloprost. PGF2alpha dose-dependently enhanced DNA synthesis and cell proliferation in the presence of insulin, with an EC50 of 0.1 muM. This eicosanoid potentiated the effects of platelet-derived growth factor (PDGF) or low concentrations of serum. Maximum stimulatory potency was about one-third that of PDGF. Removal of PGF2alpha after short-term stimulation (30 min) did not reverse its mitogenic effect. Iloprost had no effect on DNA synthesis of quiescent cells, but potently inhibited growth stimulated by various concentrations of fetal serum. PG released within the glomerular microcirculation may play a regulatory role in both normal and deranged mesangial cell growth.1

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