Transforming growth factor-β1 inhibits human keratinocyte proliferation by upregulation of a receptor-type tyrosine phosphatase R-PTP-κ gene expression

Abstract

We studied regulation of a receptor-type tyrosine phosphatase R-PTP-(κ) gene expression in a human keratinocyte cell line, HaCaT. Addition of TGF-B1 to the HaCaT cells markedly induced the expression of R-PTP-(κ) mRNA in a time- and dose-dependent manner. The induction of R-PTP-(κ) mRNA expression was observed at a dose as low as 0.02 ng/ml TGF-B1 and reached a peak at 2 ng/ml TGF-B1 after 6 h treatment. The TGF-B1-induced R-PTP-(κ) mRNA expression was suppressed by sodium orthovanadate, a tyrosine phosphatase inhibitor, and H7, a serine/threonine kinase inhibitor, but not by genistein, a tyrosine kinase inhibitor, In addition, the inducing effect is not dependent on de novo protein synthesis. Taken together, these results suggest that TGF-β1 inhibits the human keratinocyte proliferation in vitro, possibly through induction of R-PTP-(κ)K gene expression.