MECHANICAL STRETCH RELAXATION OF CULTURED RAT MESANGIAL CELLS INDUCESPROTOONCOGENES AND CYCLOOXYGENASE/

In cultured rat glomerular mesangial cells, continuous cycles of stret ching and relaxation (stretch/relaxation) stimulate cell proliferation , protein synthesis, and prostaglandin production. We examined regulat ion of gene expression that may underlie these alterations in cell fun ctions. Stretch/relaxation caused time-dependent induction of the imme diate early genes, c-fos and zif 268/egr-1, with maximal increases occ urring between 15 and 30 min. The mitogen-inducible prostaglandin G(2) /H-2 synthase (PGH(2)S-2) gene was also induced within 30 min of stret ch/relaxation, with concomitant increases in the immunoreactive PGH(2) S-2 protein. These gene inductions were preceded by transient transloc ation of protein kinase C activity from cytosol to membrane as well as by increases in Ca-45(2+) uptake and total cellular calcium content. The stretch/ relaxation-induced expression was suppressed by protein k inase C inhibition, whereas less profound inhibition was observed with inhibition of calcium influx in low (100 nM) calcium buffer. These fi ndings indicate that in mesangial cells mechanical stress induces expr ession of the protooncogenes and the mitogen-inducible cyclooxygenase primarily through protein kinase C-dependent mechanisms.