Effect of activated canonical wnt/p-catenin/tcf7l2 signaling pathway in type 1 diabetic cardiomyopathy / 中国药理学通报

ABSTRACT

Aim To determine the role of Wnt/β-catenin/TCF7L2 pathway in diabetic cardiomyopathy.Methods A model of type 1 diabetes mellitus was established by intraperitoneal injection of streptozotocin(STZ)into 7 or 8-week old C57BL/6 mice.After four weeks, the diabetic animals were divided into three groups with seven to eight in each:diabetes mellitus(DM), diabetes injected with β-catenin inhibitor iCRT14(2.5, 5 mg·kg-1).After continuous intrap-eritoneal administration for 8 weeks, heart samples were stained with HE and examined under light microscopy.Expressions and distributions of β-catenin and TCF7L2 in myocardium were detected by immunohistochemistry.Protein levels of β-catenin, Tcf7l2 were detected by Western blot.mRNA levels of β-catenin, Tcf7l2, Nppa and c-Myc were detected by qPCR.Results The myocardial cells in DM were relatively disordered and the size of the nucleus was irregular.Western blot and immunohistochemistry data showed that the expressions of β-catenin and TCF7L2 in heart with DM increased, while those in nucleus of the cardiomyocytes significantly increased.qPCR showed that the mRNA expression of β-catenin downstream target c-Myc and cardiac hypertrophy marker Nppa were up-regulated.After injection of eight weeks with different iCRT14 doses, the cardiomyocytes were relatively regular; the protein levels of β-catenin and TCF7L2 decreased, and their expressions in nucleus decreased as well; the mRNA levels of Nppa and c-Myc markedly decreased.Conclusions Activation of canonical Wnt/β-catenin/TCF7L2 signaling pathway plays a pivotal role in diabetic cardiomyopathy; iCRT14 significantly improves the phenotype of cardiomyopathy in type 1 diabetic mice.