DECREASED TYPE-II TYPE-I TGF-BETA RECEPTOR RATIO IN CELLS DERIVED FROM HUMAN ATHEROSCLEROTIC LESIONS - CONVERSION FROM AN ANTIPROLIFERATIVETO PROFIBROTIC RESPONSE TO TGF-BETA-1

Citation
Ta. Mccaffrey et al., DECREASED TYPE-II TYPE-I TGF-BETA RECEPTOR RATIO IN CELLS DERIVED FROM HUMAN ATHEROSCLEROTIC LESIONS - CONVERSION FROM AN ANTIPROLIFERATIVETO PROFIBROTIC RESPONSE TO TGF-BETA-1, The Journal of clinical investigation, 96(6), 1995, pp. 2667-2675
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0021-9738
Volume
96
Issue
6
Year of publication
1995
Pages
2667 - 2675
Database
ISI
SICI code
0021-9738(1995)96:6<2667:DTTTRR>2.0.ZU;2-U
Abstract
Atherosclerosis and postangioplasty restenosis may result from abnorma l wound healing, The present studies report that normal human smooth m uscle cells are growth inhibited by TGF-beta 1, a potent wound healing agent, and show little induction of collagen synthesis to TGF-beta 1, yet cells grown from human vascular lesions are growth stimulated by TGF-beta 1 and markedly increase collagen synthesis, Both cell types i ncrease plasminogen activator inhibitor-1 production, switch actin phe notypes in response to TGF-beta 1, and produce similar levels of TGF-P activity, Membrane cross-linking of I-125-TGF-beta 1 indicates that n ormal human smooth muscle cells express type I, II, and III receptors, The type II receptor is strikingly decreased in lesion cells, with li ttle change in the type I or III receptors, RT-PCR confirmed that the type LI TGF-beta 1 receptor mRNA is reduced in lesion cells, Transfect ion of the type II receptor into lesion cells restores the growth inhi bitory response to TGF-P1, implying that signaling remains responsive, Because TGF-P1 is overexpressed in fibroproliferative vascular lesion s, receptor-variant cells would be allowed to grow in a slow, but unco ntrolled fashion, while overproducing extracellular matrix components, This TGF-beta 1 receptor dysfunction may be relevant for atherosclero sis, restenosis, and related fibroproliferative diseases.