The impact of 1,25-dihydroxyvitamin D3 on the expression of connective tissue growth factor and transforming growth factor-β1 in the myocardium of rats with diabetes

Diabetes Res Clin Pract. 2014 May;104(2):226-33. doi: 10.1016/j.diabres.2014.01.031. Epub 2014 Feb 14.

Abstract

Aims: To define whether 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3) can protect against myocardial fibrosis and to investigate its impact on the expression of connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1) in the myocardium of rats with diabetes.

Methods: Male Sprague-Dawley rats were divided into normal (control), 1,25-(OH)2 D3 therapy, and diabetes groups. In the diabetes and 1,25-(OH)2 D3 therapy groups, type 2 diabetes models were established using a high-fat, high-sugar diet and streptozotocin. Rats in the 1,25-(OH)2 D3 therapy group were also treated with 1,25-(OH)2 D3. After 6 weeks, the body weight, cardiac weight, cardiac weight index, plasma glucose, lactic dehydrogenase (LDH) and creatine kinase (CK) were measured; morphological changes in the myocardium were observed using microscopy following hematoxylin-eosin and Masson staining. CTGF and TGF-β1 expressions in the myocardium were detected using immunohistochemistry staining and reverse transcription polymerase chain reaction.

Results: The body and cardiac weights of the rats in the diabetes and 1,25-(OH)2 D3 group were lower, but the cardiac weight index, plasma glucose, LDH and CK were higher compared with the control group (P<0.05). The body weight and plasma glucose, LDH and CK were decreased in 1,25-(OH)2 D3 group compared with the diabetes group (P<0.05). Pathological changes in the 1,25-(OH)2 D3 group were milder than the diabetes group. CTGF and TGF-β1 expression in the diabetes and 1,25-(OH)2 D3 groups were increased significantly, but in the 1,25-(OH)2 D3 group were significantly lower than diabetes group at the mRNA level.

Conclusion: 1,25-(OH)2 D3 had a partially protective effect on myocardial fibrosis of diabetic rats, which might inhibit CTGF and TGF-β1 expression in the myocardial tissues.

Keywords: 1,25-Dihydroxyvitamin D3; Connective tissue growth factor; Diabetes mellitus; Myocardial fibrosis; Transforming growth factor-β(1).

MeSH terms

  • Animals
  • Calcitriol / pharmacology*
  • Cardiomyopathies / genetics
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / prevention & control*
  • Connective Tissue Growth Factor / biosynthesis
  • Connective Tissue Growth Factor / genetics*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / metabolism
  • Fibrosis / metabolism
  • Fibrosis / prevention & control
  • Gene Expression Regulation / drug effects*
  • Immunohistochemistry
  • Male
  • Myocardium / metabolism*
  • RNA / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Spectrophotometry
  • Transforming Growth Factor beta1 / biosynthesis
  • Transforming Growth Factor beta1 / genetics*
  • Vitamins / pharmacology

Substances

  • Transforming Growth Factor beta1
  • Vitamins
  • Connective Tissue Growth Factor
  • RNA
  • Calcitriol