The lncRNA Sros1 is involved in the development of cardiac fibrosis by regulating the TGF-β/SMAD2/3 signaling cascade

Abstract

Aim: Myocardial fibrosis is one of the common pathophysiological mechanisms of heart failure (HF) caused by various etiologies. Interferon (IFN)-γ plays a key role in the body's defense against pathogen infection and antitumor and adaptive immune responses. However, long-term treatment with IFN-γ is closely related to an increased risk of cardiomyocyte necrosis and myocardial fibrosis. A recent study found that the long noncoding RNA Sros1（Sros1） can enhance IFN-γ when inducibly degraded or genetically lost. This study aimed to explore whether Sros1 plays a role in the incidence and development of cardiac fibrosis and HF. Methods: Sirius red staining, Masson staining and the expression of proteins related to myocardial fibrosis in Sros1 gene-deleted (Sros1-/-) mice and wild-type (WT) mice were compared. Changes in Sros1 in the heart and the expression of molecules related to myocardial fibrosis in both WT mice and Sros1-/- mice with chronic isoproterenol infusion (ISO) were observed. The expression levels of proteins related to myocardial fibrosis and the TGF-β/SMAD signaling pathway in cardiac fibroblasts overexpressing the Sros1 by lentivirus were detected. Results: Both Sirius red and Masson staining, as well as the expression of TGF-β/SMAD signaling pathway genes, showed increased cardiac fibrosis in Sros1-/- mice. The Sros1 gene significantly decreased in the hearts of the WT mice with ISO infusion 28 days after. Compared with that of the WT ISO model, the myocardial fibrosis of the Sros1-/- ISO model was significantly increased, as well as genes of the TGF-β/SMAD signaling pathway were elevated. Overexpression of the Sros1 by lentivirus in cardiac fibroblasts decreased the ISO-induced and TGF-β-induced expression of proteins related to myocardial fibrosis and the TGF-β/SMAD signaling pathway. Conclusion: Cardiac fibrosis was increased in Sros1-/- mice. The elevation of cardiac fibrosis in the Sros1-/- ISO group was more obvious and may be mediated through the TGF-β/SMAD signaling pathway.