Yixiao Formula Suppresses Myocardial Fibrosis Through UpregulatingmiR-133a and Downregulating TGF-β/Smads Signal...

Yixiao formula (YXF), a traditional Chinese herbal medicine, has demonstrated clinical efficacy in alleviating symptoms of diabetic cardiomyopathy (DCM). The therapeutic mechanism underlying YXF's effects on DCM remains poorly understood. Myocardial fibrosis is a key pathogenic mechanism in DCM, and previous studies have indicated that miR-133a may be involved in its progression. Given that the TGF-β/Smads signaling pathway is a well-established mediator of myocardial fibrosis, investigating the mechanistic role of YXF through miR-133a and the TGF-β/Smads pathway warrants further exploration.

The main objective of this study is to investigate the potential contribution of the TGF-β/Smads pathway to the effects of YXF, as well as the role of miR133a, through in vivo DCM models and in vitro experiments.

Spontaneously diabetic KKAy mice were used to establish a DCM model by continuous high-fat feeding, with C57BL/6 mice as controls. Echocardiography, body weight, and blood glucose data were collected every 4 weeks to examine the effects of YXF on blood glucose levels and changes in cardiac function and structure in DCM mice. Immunohistochemistry, RT-qPCR, and western blot were used to detect the expression levels of the TGF-β/Smads pathway. Additionally, the potential molecular mechanism of YXF in mouse cardiac fibroblasts (MCFs) was investigated by knocking down miR-133a.

YXF improved fasting blood glucose levels in DCM mice, promoted cardiac diastolic function, upregulated miR133a, and inhibited the expression of the TGF-β/Smads pathway. Furthermore, when miR133a inhibitors were transfected under YXF intervention, we found that YXF's inhibitory effect on the TGF-β/Smads pathway was weakened.

Through this study, we found that YXF can increase miR133a and inhibit the expression of the TGF-β/Smads pathway, thereby inhibiting myocardial fibrosis and exerting a protective effect on DCM.