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

Abstract

Background To investigate the role of circNFIB in the alleviation of myocardial fibrosis by endogenous sulfur dioxide (SO2). Methods 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. Results 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. Conclusion Endogenous SO2 promotes circNFIB expression, which inhibits the Wnt/β-catenin and p38 MAPK signaling pathways, consequently alleviating myocardial fibrosis.

Non-coding RNAs in the pathophysiology of heart failure with preserved ejection fraction

“…Furthermore, circNFIB overexpression inhibited CF proliferation based on TGF-β stimulation, whilst inhibition of circNFIB promoted proliferation ( 232 ). circNFIB was found to mitigate myocardial fibrosis induced by SO 2 through suppression of the Wnt/β-catenin and p38 MAPK signaling pathways ( 233 ). circNFIB overexpression could lay a new foundation for a novel option in treating HFpEF.…”

Elucidating the Molecular Pathways and Therapeutic Interventions of Gaseous Mediators in the Context of Fibrosis

“…A specific study has outlined the effectiveness of SO 2 in mitigating myocardial fibrosis in diabetic murine models, suggesting that the underlying mechanism involves the attenuation of apoptosis and endoplasmic reticulum stress (ERS) through the suppression of the Hippo-MST signaling pathway [109] (Figure 5). Additionally, it has been demonstrated that endogenous SO 2 enhances the expression of cir-cNFIB, a circular RNA, which in turn inhibits the Wnt/β-catenin and p38 MAPK signaling cascades, thus alleviating the progression of myocardial fibrosis [138] (Figure 5). Another study revealed that endogenous SO 2 might inhibit the ERK signaling pathway to slow myocardial fibroblast proliferation and migration [139].…”