Knockdown of ANGPTL2 reduces transforming growth factor-β1-induced fibrogenesis in cardiac fibroblasts

Angiopoietin-like 2 (ANGPTL2) is a member of ANGPTL family and plays important roles in various inflammatory diseases, tumorigenesis and fibrosis. However, the role of ANGPTL2 in cardiac fibrosis remains unclear. Thus, the objective of this study was to investigate the role of ANGPTL2 in cardiac fibrosis. Cardiac fibroblasts (CFs) were treated with TGF-beta 1 for different times. The expression of ANGPTL2 was detected by qRT-qPCR and western blot. In addition, CFs were transfected with si-ANGPTL2 or scramble and then stimulated with 10 ng/ml TGF-beta 1. Cell proliferation was determined by the colony formation assay. The expression of a-SMA, collagen I, p-Smad3 and Smad3 was analyzed by western blot. Our results demonstrated for the first time that ANGPTL2 mRNA and protein levels were significantly up-regulated in transforming growth factor beta 1 (TGF-beta 1)-stimulated CFs. In addition, knockdown of ANGPTL2 inhibited cell proliferation and ECM expression in TGF-beta 1-stimulated CFs. Further mechanism study indicated that knockdown of ANGPTL2 significantly inhibited the TGF-beta 1-induced p-Smad3 in CFs. In conclusion, this study showed that knockdown of ANGPTL2 inhibited cell proliferation and ECM expression in TGF beta 1-stimulated CFs through interfering with TGF-beta 1/Smad3 signaling pathway. Thus, ANGPTL2 may be a potential therapeutic target for cardiac fibrosis.