TYPE-V COLLAGEN IS AN EPITHELIAL-CELL CYCLE INHIBITOR THAT IS INDUCEDBY AND MIMICS THE EFFECTS OF TRANSFORMING-GROWTH-FACTOR BETA-1

The regulation of epithelial cell cycle progression by extracellular m atrix proteins was investigated in mink lung epithelial cells (Mv1Lu c ells) and primary human keratinocytes. Exogenous type V collagen was a ble to mimic all of the inhibitory effects of type 1 transforming grow th factor beta (TGF-beta 1). No significant inhibitory effect was obse rved with collagen types I, III, and IV; laminin; or fibronectin, The type V collagen used was not contaminated with TGF-beta s. TGF-beta 1 increased the rate of type V collagen protein secretion in Mv1Lu cells , which occurred coincident with DNA synthesis inhibition, Both TGF-be ta 1 and type V collagen inhibited retinoblastoma protein phosphorylat ion and the expression of cyclin-dependent kinase (cdk) 4 and cdk2, bu t not p27(Kip) expression. Mv1Lu cells constitutively expressing the S V40 T antigen or cdk4 were resistant to the inhibitory effects of both TGF-beta 1 and type V collagen. Our results demonstrate that type V c ollagen is a novel and specific epithelial cell cycle inhibitor and su ggest that it may act as an autocrine mediator of the inhibitory effec ts of TGF-beta 1.