Meng Ke, Cai Huabo, Cai Simin, Hong Yucai, Zhang Xiaoming
Department of Anatomy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Emergency Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Front Cell Dev Biol. 2021 Mar 22;9:644160. doi: 10.3389/fcell.2021.644160. eCollection 2021.
Accumulating evidence suggested that bone marrow mesenchymal stem cells (BMSCs) have therapeutic potential for diabetes and heart diseases. However, the effects of BMSC on reducing myocardial fibrosis need to be optimized. This study aimed to investigate the mechanism of adiponectin (APN) modified BMSCs on myocardial fibrosis in diabetic model and . The high-fat diet combined with streptozotocin (STZ) injection were used to induced diabetic rat model. H9c2 cells were cultured under a high glucose medium as model. The BMSCs were modified by APN plasmid or APN small interfering RNA (siRNA), then transplanted to the diabetic rats by a single tail-vein injection, or co-cultured with H9c2 cells. We demonstrated that diabetic rats showed typical diabetic symptoms, such as decreased cardiac function, accumulation of pathological lesions and collagen expression. However, these impairments were significantly prevented by the APN modified BMSCs treatment while no effects on APN siRNA modified BMSCs treated diabetic rats. Moreover, we confirmed that APN modified BMSCs could attenuate the expression of TGF-beta1/smad to suppress the myocardial fibrosis in the diabetic rats and high glucose induced H9c2 cells. The present results for the first time showed that APN modified BMSCs exerted protection on cardiac fibrosis via inhibiting TGF-beta1/smad signal pathway in diabetic rats. Our findings suggested that APN modified BMSCs might be a novel and optimal therapy for the diabetic cardiomyopathy in future.
越来越多的证据表明，骨髓间充质干细胞（BMSCs）对糖尿病和心脏病具有治疗潜力。然而，BMSC在减轻心肌纤维化方面的效果需要优化。本研究旨在探讨脂联素（APN）修饰的BMSCs对糖尿病模型心肌纤维化的作用机制。采用高脂饮食联合链脲佐菌素（STZ）注射诱导糖尿病大鼠模型。将H9c2细胞在高糖培养基中培养作为模型。用APN质粒或APN小干扰RNA（siRNA）修饰BMSCs，然后通过单尾静脉注射将其移植到糖尿病大鼠体内，或与H9c2细胞共培养。我们发现糖尿病大鼠表现出典型的糖尿病症状，如心脏功能下降、病理损伤积累和胶原蛋白表达增加。然而，APN修饰的BMSCs治疗可显著改善这些损伤，而对APN siRNA修饰的BMSCs治疗的糖尿病大鼠则无影响。此外，我们证实APN修饰的BMSCs可减弱TGF-β1/smad的表达，以抑制糖尿病大鼠和高糖诱导的H9c2细胞中的心肌纤维化。目前的结果首次表明，APN修饰的BMSCs通过抑制糖尿病大鼠的TGF-β1/smad信号通路对心脏纤维化发挥保护作用。我们的研究结果表明，APN修饰的BMSCs可能是未来治疗糖尿病性心肌病的一种新型且最佳的疗法。
