Effect of activated canonical Wnt/β-catenin/TCF7L2 signaling pathway in type 1 diabetic cardiomyopathy

QIU Xiao-xia1,2 LI Yi-lang1,2 LIANG Guan-feng1,2 ZHANG Gui-ping1,2 LUO Jian-dong YUAN Wen-chang2 HOU Ning1

(1.Dept of Pharmacology, Guangzhou Medical University, Guangzhou, China 511436)
(2.Dept of Clinical Lab, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 510000)
【Knowledge Link】glucagon; intercalated disc

【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 and 5 mg·kg−1). After continuous intraperitoneal administration for 8 weeks, heart samples were stained with HE and examined under light microscopy. The expression and distributions of β-catenin and TCF7L2 in myocardium were detected by immunohistochemistry. The protein levels of β-catenin, TCF7L2 were detected by Western blot. The 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. The Western blot and immunohistochemistry data showed that the expression of β-catenin and TCF7L2 in heart with DM increased, while that 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 was upregulated. 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 expression 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.

【Keywords】 diabetes; streptozotocin; cardiac hypertrophy; Wnt/β-catenin/TCF7L2 signaling pathway; iCRT14; c-Myc; Nppa;

【DOI】

【Funds】 National Natural Science Foundation of China (81773720, 81402928) Guangzhou Science and Technology Plan Project (201804010490) Guangzhou Education Research Project (1201610064)

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This Article

ISSN:1001-1978

CN: 34-1086/R

Vol 35, No. 08, Pages 1104-1109

August 2019

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Abstract

  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References