ZFP36 inhibits the pro‐apoptotic effects of transforming growth factor β1 on mitral valve interstitial cells via the GTP‐binding protein 6 pathway in mitral valve prolapse

Abstract The objective of this work was to investigate the role of ZFP36 in mitral valve prolapse (MVP). Mitral valve and plasma were collected to assess the expression of ZFP36, transforming growth factor β (TGF‐β), collagen and elastin and apoptosis rates. Mitral valve interstitial cells (MICs) were transfected with ZFP36 plasmids to observe changes in the secretion of collagen, elastin and matrix metalloproteinases (MMPs) and apoptosis rates. MICs were exposed to TGF‐β1 to evaluate the changes in expression of collagen, elastin, MMPs and ZFP36 and apoptosis. Subsequently, after transfection with ZFP36 plasmid, exogenous TGF‐β1 was added to the MICs, and the secretion of collagen, elastin and MMPs and apoptosis rate were re‐evaluated. Finally, transcriptome and RNA immunoprecipitation (RIP) sequencing was conducted to identify downstream genes of TGF‐β1 that could bind to ZFP36. Patients with MVP showed elevated levels of TGF‐β1 in plasma and increased rates of apoptosis, along with higher expression of ZFP36, TGF‐β1, collagen and elastin in the prolapsed valve. Overexpression of ZFP36 in MICs did not significantly alter the secretion of collagen or elastin or apoptosis rates. TGF‐β1 promoted apoptosis of MICs, increased the secretion of collagen, elastin, MMP‐3,9, ZFP36 and reduced the expression of MMP‐1,2,13. Moreover, overexpression of ZFP36 inhibited the effects of TGF‐β1 on MICs. Co‐analysis of transcriptome and RIP sequencing identified three genes: CFAP184, GTP binding protein 6 (GBP6) and HERC6. Knockdown of GBP6 reduced the pro‐apoptotic effects of TGF‐β1 on MICs. ZFP36 exerts a protective role in MVP by inhibiting the effects of TGF‐β1 on MICs. Notably, ZFP36 can mitigate the pro‐apoptotic effects of TGF‐β1 on MICs through the GBP6 pathway.