Regulation of cardiac fibroblast cellular function by leukemia inhibitory factor.
BACKGROUND
Previous studies have shown that leukemia inhibitory factor (LIF) provokes hypertrophic and cytoprotective effects in cardiac myocytes. However, the effects of LIF in cardiac fibroblasts are not known. Given that the cardiac fibroblast is the most abundant cell type in the heart, we sought to examine the functional effects of LIF on cardiac fibroblasts in vitro.


RESULTS
Short-term LIF stimulation (24h) had no effect on fibroblast proliferation and/or cell differentiation. However, longer-term LIF stimulation (48-72h) increased fibroblast proliferation, and significantly inhibited cardiac fibroblast differentiation into myofibroblasts. Moreover, 72h of LIF stimulation significantly reduced collagen content in cardiac fibroblasts cultures, as well as decreased MMP activity in fibroblast culture supernatants.


CONCLUSIONS
The results of this study suggest that LIF stimulation down-regulates several key components of the remodeling process, including collagen content and matrix metalloproteinase (MMP) activation, and thus suggest that LIF may play an important autocrine/paracrine role in preventing excessive extracellular matrix remodeling following acute myocardial injury.
Wang
Feng
F
Winters Center for Heart Failure Research, Baylor College of Medicine, 6565 Fannin Street, Houston, TX 77030, USA.
Trial
JoAnn
J
Diwan
Abhinav
A
Gao
Feng
F
Birdsall
Holly
H
Entman
Mark
M
Hornsby
Peter
P
Sivasubramaniam
Natarajan
N
Mann
Douglas
D
D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors
D000199:Actins; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D003094:Collagen; D004247:DNA; D020778:Matrix Metalloproteinase 2