TIMP1 and heart failure: Specifically, TIMP1 induced the interaction between CD63 (a cell surface receptor of TIMP1) and integrin-β1 in fibroblasts, which initiated the activation and nuclear translocation of Smad2/3 and β-catenin and subsequent collagen synthesis.232 Moreover, periostin, an ECM protein that is mainly secreted by osteoblasts and fibroblasts, was upregulated in human samples of chronic heart failure and angiotensin II-induced heart failure.