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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/H1053    most recent 00935.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Drobic, V. Articles by Dixon, I. M. C. Search for Related Content PubMed PubMed Citation Articles by Drobic, V. Articles by Dixon, I. M. C.

Differential and combined effects of cardiotrophin-1 and TGF-₁ on cardiac myofibroblast proliferation and contraction

Institute of Cardiovascular Science, St. Boniface General Hospital Research Centre, Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

Submitted 29 August 2006 ; accepted in final form 30 April 2007

Myofibroblasts respond to an array of signals from mitogens and cytokines during the course of wound healing following a myocardial infarction (MI), and these signals may coordinate ventricular myofibroblast proliferation. Furthermore, myofibroblasts are contractile and contribute to wound contraction by imparting mechanical tension on surrounding extracellular matrix. Although TGF-₁, CT-1, and PDGF-BB participate in various stages of post-MI wound healing, their combined net effect(s) on myofibroblast function is unknown. We investigated myofibroblast proliferation, expression of cell cycle proteins, and contractile function of cells treated with TGF-₁ and/or CT-1. We confirmed that TGF-₁ (10 ng/ml) suppresses proliferation of these cells, whereas CT-1 (10 ng/ml) and, for comparative purposes, PDGF-BB (1 ng/ml) treatments were associated with proliferation. Specific TGF-₁ treatment ablated CT-1-induced myofibroblast proliferation. TGF-₁ effects were specific, as they were suppressed by either TGF--neutralizing antibody or viral Smad7 overexpression. TGF-₁ treatment also increased expression of p27 and decreased expression of cyclin E and Cdk2 in primary cells. CT-1 (10 ng/ml) treatment of myofibroblasts had no effect on collagen gel deformation versus controls, whereas TGF-₁ (10 ng/ml) and PDGF (10 ng/ml) treatments were associated with significant cell contraction; again, TGF-₁-mediated contraction was unaffected by CT-1. Alone, CT-1 and TGF-₁ treatments exert opposing effects on myofibroblast function, whereas in combination TGF-₁-mediated effects supersede those of CT-1 (and PDGF-BB). Thus TGF-₁ and CT-1 exert differential effects on myofibroblast proliferation and contraction in vitro, and we suggest that a balance of these effects may be important for the execution of normal cardiac wound healing.

transforming growth factor-₁; Smad7

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