Myocardial fibrosis represents a maladaptive response to some pathological stimulus affecting the heart's functions, predisposing to arrhythmia and ultimately heart failure (HF). Stathmin 1 (Stmn1) is a core protein in regulating the formation of the mitotic spindle. Although the dysregulation of Stmn1 has been confirmed to be related to the occurrence of kidney or liver fibrosis, the role of Stmn1 in HF remains obscure. In this study, bioinformatic analysis (GSE150736) of myocardial tissues from HF patients suggested that Stmn1 was significantly upregulated compared with healthy controls. The consistent results were also observed in the heart tissues of the rat model of HF. Furthermore, we demonstrated that Adenovirus-mediated overexpression of Stmn1 in the peri-infarct border zone area significantly improved cardiac fibrosis and collagen deposition, as evidenced by the decreased expression of transforming growth factor-beta1 (TGF-β1), collagen IV, and alpha-smooth muscle actin in heart tissues. In vitro, overexpression of Stmn1 reduced the production and deposition of collagen in cardiac fibroblasts (CFs) induced by TGF-β1, and thus inhibited the activation of CFs into myofibroblasts. Mechanistically, upregulation of Stmn1 significantly suppressed the phosphorylation of p38 both in vivo and in vitro. Moreover, we demonstrated that Stmn1 was transcriptionally regulated by the cohesin and CCCTC-binding factor (Ctcf) and functionally mediated the cardioprotective effects of Ctcf. Collectively, this work established Stmn1 as a promising therapeutic target for myocardial fibrosis in HF.
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