Cardiac fibroblasts are predisposed to convert into myocyte phenotype: specific effect of transforming growth factor beta.
Cardiac fibroblasts are mainly responsible for the synthesis of major extracellular matrix proteins in the heart, including fibrillar collagen types I and III and fibronectin. In this report we show that these cells, when stimulated by transforming growth factor beta 1 (TGF-beta 1), acquire certain myocyte-specific properties. Cultured cardiac fibroblasts from adult rabbit heart were treated with TGF-beta 1 (10-15 ng/ml) for different periods of time. Northern hybridization analysis of total RNA showed that cells treated with TGF-beta 1 for 24 hr expressed mRNA corresponding to sarcomeric actin mRNA. Immunofluorescence staining and light microscopy showed that cultured cardiac fibroblasts treated with TGF-beta 1 became stained with a monoclonal antibody to muscle-specific actin. After treatment of quiescent cells with TGF-beta 1, cell proliferation (as measured by [3H]thymidine incorporation) was moderately increased (1.5-fold, P less than 0.001). NIH 3T3 cells and human skin fibroblasts, treated with TGF-beta 1, did not express sarcomeric actin mRNA. Treatment of cardiac fibroblasts with the mitogenic agent phorbol 12-myristate 13-acetate or with norepinephrine, angiotensin II, or interleukin 1 beta did not induce myocyte-specific actin mRNA. Cultured cardiac fibroblasts at the subconfluent stage, when exposed to TGF-beta 1 in the presence of 10% fetal bovine serum, gave rise to a second generation of slowly growing cells that expressed muscle-specific actin filaments. Our findings demonstrate that cardiac fibroblasts can be made to differentiate into cells that display many characteristics of cardiac myocytes. TGF-beta 1 seems to be a specific inducer of such conversion.
Eghbali
M
M
Michael Reese Hospital and Medical Center, Department of Medicine, University of Chicago, IL 60616.
Tomek
R
R
Woods
C
C
Bhambi
B
B
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D000199:Actins / Q000032:analysis / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015342:DNA Probes; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology*; D009206:Myocardium / Q000166:cytology*; D009218:Myosins / Q000032:analysis / Q000235:genetics; D015345:Oligonucleotide Probes; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011817:Rabbits; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000199:Actins; D015342:DNA Probes; D015345:Oligonucleotide Probes; D016212:Transforming Growth Factor beta; D012313:RNA; D009218:Myosins; D013936:Thymidine