Regulation of Cardiac Fibroblast Cellular Function by Leukemia Inhibitory Factor

F. Wang, J. Trial, J. A. Diwan, F. Gao, H. H. Birdsall, M. L. Entman, P. J. Hornsby, N. Sivasubramaniam and D. L. Mann, Regulation of Cardiac Fibroblast Cellular Function by Leukemia Inhibitory Factor. Journal of Molecular and Cellular Cardiology (2002) 34, 1309–1316. 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 (24 h) had no effect on fibroblast proliferation and/or cell differentiation. However, longer-term LIF stimulation (48–72 h) increased fibroblast proliferation, and significantly inhibited cardiac fibroblast differentiation into myofibroblasts. Moreover, 72 h of LIF stimulation significantly reduced collagen content in cardiac fibroblasts cultures, as well as decreased MMP activity in fibroblast culture supernatants. Conclusion: 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.