Cardiac fibroblast-specific expression of IL-37 confers the pr-otective effects on fibrosis in diabetic cardiomyopathy mice by regulating SOCS3-STAT3 axis
Qing-Yu HUANG1
Jian LI1
Tong-Qing CHEN2
Yi-Ming WANG1
Xiao-Yan SHEN2
Hai-Ming SHI1
Xin-Ping LUO1
Bo JIN1
Yan YOU2
Bang-Wei WU1
1.Department of Cardiology,Huashan Hospital,Fudan University,Shanghai,China2.Department of Pharmacology &the Key Laboratory of Smart Drug Delivery,Ministry of Education,School of Pharmacy,Fudan University,Shanghai,China
摘要：Background Human interleukin(IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppress-ive attributes.It has been demonstrated extensive beneficial effects on various diseases;however,its role in the pathogenesis of diabetic cardiomyopathy(DCM)remains unclear.
Methods In vivo,DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibro-blasts(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 echocardio-graphy.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 regulat-or 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 inactiva-tion and may be considered as a potential therapeutic agent for DCM.
机标关键词：expressionfibroblastfibrosisspecificaxismicecardiaccardiomyopathy
论文发表日期：2024-11-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 1060-1070 )