University of California, San Francisco
Collagen Turnover in Aging and Fibrosis
Despite extensive research, the pathogenesis of tissue fibrosis is still incompletely understood. Resolution of fibrosis is impaired in aging and this impairment may explain why age is the most important risk factor for fibrotic diseases such as Idiopathic Pulmonary Fibrosis. Excess collagen deposition in tissues is an integral part of the development of fibrotic diseases and can be seen as an imbalance between collagen production and collagen degradation. In mouse models, the cellular-based pathways of collagen degradation have been shown to be important in promoting resolution of pulmonary fibrosis. Yet, the specific regulatory mechanisms controlling collagen degradation in cells remain incompletely understood. Currently, there are no approved therapies that target pathways to augment degradation of fibrotic tissue even though this would have a significant impact on patients with established fibrotic disease. The unifying hypothesis of this grant is that the age-related downregulation of Endo180 may at least in part explain the impaired resolution of fibrosis in aging. A better understanding of the regulatory mechanisms that govern collagen degradation and Endo180 expression may pave the way for new therapeutic strategies in fibrosis that target the collagen degradative machinery in order to promote resolution of fibrosis.