Cardiac fibroblast-specific expression of IL-37 ameliorated cardiac dysfunction and reduced collagen production in diabetic cardiomyopathy mice by promoting SOCS3-mediated JAK2-STAT3 inactivation.
Does cardiac fibroblast-specific expression of IL-37 improve cardiac function and reduce fibrosis in diabetic cardiomyopathy mice?
IL-37 exerts antifibrotic effects and improves cardiac function in diabetic cardiomyopathy by promoting SOCS3-mediated JAK2-STAT3 inactivation.
Background: Human interleukin (IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes. It has been demonstrated extensive beneficial effects on various diseases; however, its role in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. Methods: , DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts (CFs) specific hIL-37b overexpression mice (IL-37-Tg). In vitro, primary mouse CFs were isolated from the hearts of adult mice and cultured with high levels of glucose and palmitic acid. Cardiac function of the mice was assessed using echocardiography. Masson staining, immunofluorescence, western blot and RT-PCR assays were employed to evaluate the expression of cardiac fibrosis and SOCS3-JAK2-STAT3 signaling pathway-related proteins. Results: In this study, we found that CFs specific IL-37-Tg significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting the JAK2-STAT3 axis, as evidenced by the decreased levels of p-JAK2 and p-STAT3 in the heart of CFs specific IL-37-Tg DCM mice. The beneficial effects of IL-37 were consistently observed in CFs treated with high glucose (HG) and palmitic acid (PA). Moreover, we also discovered that the presence of IL-37 increased the expression of SOCS3, a crucial regulator of JAK/STAT signaling, in DCM mice and HG and PA-treated CFs. Finally, the anti-fibrotic action of IL-37 in HG and PA-treated CFs was abolished when either SOCS3 was genetically knocked down or JAK2/STAT3 was pharmacologically activated. Conclusions: Our findings indicate that IL-37 exerts its antifibrotic effect by promoting SOCS3-mediated JAK2-STAT3 inactivation and may be considered as a potential therapeutic agent for DCM.
Huang et al. (2024) studied Diabetic cardiomyopathy. Cardiac fibroblast-specific hIL-37b overexpression vs. Wild-type mice was evaluated on Cardiac dysfunction and fibrosis. Cardiac fibroblast-specific expression of IL-37 ameliorated cardiac dysfunction and reduced collagen production in diabetic cardiomyopathy mice by promoting SOCS3-mediated JAK2-STAT3 inactivation.