CONTROL OF VASCULAR FIBROSIS AND COLLAGEN DEPOSITION BY NOVEL REGULATOR, CTHRC-1

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The response to injury, whether it is restenosis after balloon angioplasty, or pulmonary or renal fibrosis due to chronic inflammation, results in increased accumulation of extracellular matrix (ECM) components with detrimental effects on tissue structure and function. This response involves the activation of fibroblasts termed myofibroblasts based on their characteristic expression of smooth muscle alpha-actin. As part of this wound healing response, these myofibroblasts proliferate, migrate, and produce abundant ECM including collagen type I and type III, as well as other ECM molecules. Dr. Lindner has identified a novel secreted 28 kDa protein called Collagen triple helix repeat containing 1 (Cthrc1) in a screen of differentially expressed sequences in balloon-injured versus normal vessels. Cthrc1 is highly expressed in medial smooth muscle cells and adventitial fibroblasts two weeks after vascular injury but expression declines by 4 weeks post-injury. Over expression of Cthrc1 in vascular smooth muscle cells results in decreased cell migration and reduced collagen matrix deposition. These exciting results suggest that Cthrc1 may have a regulatory role in the fibrotic response to injury and perhaps chronic inflammation. The proposed studies will provide significant new insights into the regulation of the fibrotic response in several organ systems, most importantly the vessel wall. These studies have translational potential for antifibrotic strategies.