TGF-beta 1 signaling controls retinal pericyte contractile protein expression

To define the role of transforming growth factor-beta 1 (TGF-beta 1) 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 (DNT beta RII). While TGF-beta 1 blocks pericyte proliferation and induces the expression of vascular smooth muscle contractile proteins in wild-type pericytes, DNT beta RII-bearing pericytes are neither growth inhibited by TGF-beta 1 nor do they accumulate alpha-smooth muscle actin (alpha-SMA) mRNA or protein. TGF-beta 1 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 DNT beta RII-bearing pericytes. These observations demonstrate that the TGF-beta 1 signaling pathway controls pericyte growth state and contractile phenotype.