Mechanical stretch/relaxation of cultured rat mesangial cells induces protooncogenes and cyclooxygenase.

Akai Y, Homma T, Burns KD, Yasuda T, Badr KF, Harris RC
Am J Physiol. 1994 267 (2 Pt 1): C482-90

PMID: 8074183 · DOI:10.1152/ajpcell.1994.267.2.C482

In cultured rat glomerular mesangial cells, continuous cycles of stretching and relaxation (stretch/relaxation) stimulate cell proliferation, protein synthesis, and prostaglandin production. We examined regulation of gene expression that may underlie these alterations in cell functions. Stretch/relaxation caused time-dependent induction of the immediate early genes, c-fos and zif 268/egr-1, with maximal increases occurring between 15 and 30 min. The mitogen-inducible prostaglandin G2/H2 synthase (PGH2S-2) gene was also induced within 30 min of stretch/relaxation, with concomitant increases in the immunoreactive PGH2S-2 protein. These gene inductions were preceded by transient translocation of protein kinase C activity from cytosol to membrane as well as by increases in 45Ca2+ uptake and total cellular calcium content. The stretch/relaxation-induced expression was suppressed by protein kinase C inhibition, whereas less profound inhibition was observed with inhibition of calcium influx in low (100 nM) calcium buffer. These findings indicate that in mesangial cells mechanical stress induces expression of the protooncogenes and the mitogen-inducible cyclooxygenase primarily through protein kinase C-dependent mechanisms.

MeSH Terms (14)

Animals Calcium Cell Membrane Cells, Cultured Cytosol Enzyme Induction Gene Expression Regulation Genes, Immediate-Early Glomerular Mesangium Physical Stimulation Prostaglandin-Endoperoxide Synthases Protein Kinase C Proto-Oncogenes Rats

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