Peroxisome proliferator-activated receptor-gamma activation attenuates diabetic cardiomyopathy via regulation of the TGF-β/ERK pathway and epithelial-to-mesenchymal transition.

Diabetic cardiomyopathy (DCM) is a kind of disease caused by metabolic disorders and microangiopathy. The main pathophysiological changes of DCM include fibrosis, myocardial cell apoptosis and autonomic neuropathy. Therefore, treatment aimed at these processes may benefit patients with DCM. We designed an experiment with the peroxisome proliferator-activated receptor-gamma (PPARγ) agonist GW 1929 to detect whether the activation of PPARγ could alleviate the degree of DCM. To further detect the mechanism of PPARγ in DCM, we used the PPARγ antagonist GW 9662 and ERK antagonist PD 098059 both in vitro and in vivo and found that PPARγ functioned by inhibiting ERK. We also performed Western blot, PCR, ELISA, immunohistochemistry, TUNEL assay, Sirius red staining and gelatin zymography to investigate inflammation, apoptosis, MMP activity and epithelial-to-mesenchymal transition (EMT). The results showed that the activation of PPARγ inhibited these reactions and inhibiting ERK also simulated this phenomenon. In conclusion, these results demonstrated that PPARγ activation in the diabetic myocardium of mice reduces myocardial fibrosis via regulation of the TGF-β/ERK pathway and EMT.