Elucidating the role of circNFIB in myocardial fibrosis alleviation by endogenous sulfur dioxide.

To investigate the role of circNFIB in the alleviation of myocardial fibrosis by endogenous sulfur dioxide (SO2). We stimulated cultured neonatal rat cardiac fibroblasts with transforming growth factor-β1 (TGF-β1) and developed an in vitro myocardial fibrosis model. Lentivirus vectors containing aspartate aminotransferase 1 (AAT1) cDNA were used to overexpress AAT1, and siRNA was used to silence circNFIB. The SO2, collagen, circNFIB, Wnt/β-catenin, and p38 MAPK pathways were examined in each group. In the in vitro TGF-β1-induced myocardial fibrosis model, endogenous SO2/AAT1 expression was significantly decreased, and collagen levels in the cell supernatant and type I and III collagen expression, as well as α-SMA expression, were all significantly increased. TGF-β1 also significantly reduced circNFIB expression. AAT1 overexpression significantly reduced myocardial fibrosis while significantly increasing circNFIB expression. Endogenous SO2 alleviated myocardial fibrosis after circNFIB expression was blocked. We discovered that circNFIB plays an important role in the alleviation of myocardial fibrosis by endogenous SO2 by inhibiting the Wnt/β-catenin and p38 MAPK pathways. Endogenous SO2 promotes circNFIB expression, which inhibits the Wnt/β-catenin and p38 MAPK signaling pathways, consequently alleviating myocardial fibrosis.