TGF-beta 1 signaling controls retinal pericyte contractile protein expression

To define the role of transforming growth factor-beta1 (TGF-beta1) in modulating pericyte contractile phenotype, we have ablated the TGF-beta signaling pathway by infection with a retrovirus bearing a TGF-beta type II receptor with a truncated C-terminal intracellular kinase domain (DNTbetaRII). While TGF-beta1 blocks pericyte proliferation and induces the expression of vascular smooth muscle contractile proteins in wild-type pericytes, DNTbetaRII-bearing pericytes are neither growth inhibited by TGF-beta1 nor do they accumulate a-smooth muscle actin (alpha-SMA) mRNA or protein. TGF-beta1 induces expression of the myogenic transcription factor myf-5 and the cyclin-dependent kinase inhibitor p27; we show that these signaling pathways are disrupted in the DNTbetaRII-bearing pericytes. These observations demonstrate that the TGF-beta1 signaling pathway controls pericyte growth state and contractile phenotype. (C) 2003 Elsevier Inc. All rights reserved.