Maine Medical Center, Medical Education, Maine Medical Center Research Institute
Extracellular Matrix Proteins
actinThe human aging is usually accompanied by sarcopenic obesity and increased sensitivity of tissues to stress factors. The development of approaches promoting healthy versus disease-associated aging should address these issues. CTHRC1 is a secreted protein discovered in Lindner laboratory, based on its enhanced expression in remodeling vessels. Cthrc1 null mice develop abnormalities observed in humans with aging, such as increased body fat, reduced muscle and bone mass, and reduced physical activity. Our in vitro studies have demonstrated that CTHRC1 suppresses adipogenesis by strongly decreasing the expression of pro-adipogenic transcription factors of the CEBP family and enhancing the expression of the anti-adipogenictranscription factor SOX9. We have also found that CTHRC1 stimulates cytoprotective Aktsignaling and protects endothelial cells from the stress induced by growth factor depletion. In addition, CTHRC1 protects mesencephalon-derived cells from dopamine-induced apoptosis. The antiadipogenicand cytoprotective effects of CTHRC1 support future studies aimed at assessing its ability to delay the age-related decline in physiology.
Prudovsky, Igor; Siviski, Matthew; Kacer, Doreen; Jin, Yongri; DeMambro, Victoria; Stohn, Patrizio; Pyburn, Kathleen; Berkovitch, Rachel; Makki, Alaa; and Lindner, Volkhard, "Anti-adipogenicand cytoprotectiveeffects of CTHRC1 and its potential role in the regulation of aging" (2020). Costas T. Lambrew Research Retreat 2020. 19.