Role of Discoidin Domain Receptors 1 and 2 in Human Smooth Muscle Cell-Mediated Collagen Remodeling: Potential Implications in Atherosclerosis and Lymphangioleiomyomatosis

摘要: Obstructive diseases of blood vessels and the lung are characterized by degradation synthesis new extracellular matrix (ECM) components. Regulated remodeling ECM in such as atherosclerosis lymphangioleiomyomatosis (LAM), both excessive accumulation smooth muscle cells (SMCs), is thought to be controlled part cell surface receptors for specific Discoidin domain (DDR) 1 2 represent a family tyrosine kinase collagen that activated fibrillar collagens. To test hypothesis DDR may involved SMCs vivo, we analyzed expression reverse transcriptase-polymerase chain reaction immunohistochemistry demonstrate DDR1 DDR2 up-regulated nodules LAM compared normal controls, expressed lesions atherosclerosis. In vitro, retroviral overexpression or human cultured on polymerized gels leads reduction induces metalloproteinase (MMP) at mRNA protein levels, but only enhances MMP2 activation. Moreover, increases SMC-mediated elastin vitro. Using laser microdissection, extend our studies analysis from where observe higher MMP1 Taken together, these data provide evidence potential roles regulation turnover mediated obstructive lung.