Alteration of Wnt/β-catenin signaling pathway in type 2 diabetic rats' aorta and regulation of SIRT1

YIN Mao-shan1,2 XU Shu-hong3 WANG Yan1 SUN Xiao-hui1,2 LIANG Chen1,2 LI Jie1 MU Yan-ling1

(1.Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, China 250062)
(2.School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, China 250062)
(3.China Pharmaceutical University, Nanjing, China 211198)

【Abstract】 Aim To investigate the alteration of Wnt/β-catenin signaling and sirtuins 1 in type 2 diabetic rats' aorta and clarify its role in the development of diabetes aortic disease. Methods The type 2 diabetic rat model was established by injection of streptozocin after five-week of high fat diet. The rats were randomly divided into control group, DM model group of 2 weeks, 4 weeks, 8 weeks and 12 weeks. Fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and fasting insulin (FINS) levels were tested. HE staining was used to observe the pathological changes of aortal structures. The alteration of Wnt2, β-catenin, TCF4, SIRT1 and sFRP2 in aorta was determined by Western blot and RT-PCR. Results Compared with control group, TC, TG, LDL-C levels of type 2 diabetic rats were significantly increased, HDL-C levels were significantly reduced (P < 0.01). Aortic histological analysis revealed that DM induced aortic endothelial cell vacuolar degeneration and necrosis. The expression of Wnt2 and β-catenin level increased significantly in the first 4 weeks of diabetic groups compared to control group, and that in model group of 8 weeks and 12 weeks kept in the high level and showed no significant alteration (P > 0.05). But the expression of TCF4 and SIRT1 was enhanced continuously in DM compared with control group while sFRP2 decreased in the duration of DM development. Conclusions Wnt/β-catenin signaling pathway was activated in diabetic aorta injury by regulation of SIRT1 via sFRP2. Further researches on its mechanism of action in DM aorta injury may find a new therapeutic target for the disease.

【Keywords】 Wnt2; β-catenin; TCF4; SIRT1; sFRP2; type 2 diabetes; aorta injury;

【DOI】

【Funds】 National Natural Science Foundation of China (No. 30701022) Outstanding Middle-aged and Young Scientist Research Award Fund Project of Shandong Province (No. BS2013SW008)

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This Article

ISSN:1001-1978

CN: 34-1086/R

Vol 32, No. 03, Pages 337-342

March 2016

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Abstract

  • 1 Materials and method
  • 2 Results
  • 3 Discussion
  • References