Lissette S. Velasquez1, Lillian B. Sutherland2,3, Zhenan Liu4,3, Frederick Grinnell4, Kristine E. Kamm5, Jay W. Schneider6, Eric N. Olson2, Eric M. Small1
1Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; and
2Departments of bMolecular Biology,
3University of Texas Southwestern Medical Center
4Cell Biology, and
5Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390
6Internal Medicine
Tóm tắt
Significance
Myofibroblasts are contractile smooth muscle-like cells that control tissue repair and remodeling. Inappropriate myofibroblast differentiation can cause organ fibrosis or inefficient wound healing. In this article, we demonstrate that myocardin-related transcription factor (MRTF)-A is necessary for myofibroblast differentiation. We also identify an isoxazole ring-containing small molecule that stimulates MRTF-A–dependent gene expression, myofibroblast differentiation, and wound healing. These findings suggest that targeting MRTFs pharmacologically may prove useful in treating fibrotic diseases.
