1,25(OH)2D3-mediated amelioration of aortic injury in streptozotocin-induced diabetic rats

Inflammation. 2013 Dec;36(6):1334-43. doi: 10.1007/s10753-013-9672-5.

Abstract

In this study, a single tail vein injection of streptozotocin (STZ)-induced rat model was employed to study the effects of 1,25(OH)2D3 supplementation, the active form of vitamin D, on diabetes-induced aortic injury. Aortas from different groups were assessed for histopathology, toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and nuclear factor-kappa B (NF-κB) p65 expression by hematoxylin and eosin staining, immunohistochemistry staining, reverse transcription polymerase chain reaction, and Western blot analysis. High-dose 1,25(OH)2D3 (0.3 μg/kg/day) significantly prevented diabetes-induced aortic pathological changes and collagen deposition and decreased the expression of TLR4, MyD88, and NF-κB at both mRNA and protein levels in the aorta of STZ-induced diabetic rats (P < 0.01). In vitro studies in A7r5 cells (a rat embryonic thoracic aortic smooth muscle cell line) showed that high-dose glucose (25 mmol/L) enhanced TLR4 expression at both mRNA and protein levels by fourfold and twofold, respectively, at 24 h, which were significantly diminished by 1,25(OH)2D3 (1 × 10(-7) mol/L) by 50 and 36 %, respectively. Similar effects of high-dose 1,25(OH)2D3 on the expression of MyD88 were observed. Our results indicate that vitamin D has protective effects on diabetes-induced aortic injury and attenuates the expressions of TLR4, MyD88, and NF-κB in diabetic rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / injuries
  • Aortic Diseases / drug therapy
  • Cell Line
  • Collagen / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Glucose / pharmacology
  • Male
  • Myeloid Differentiation Factor 88 / biosynthesis*
  • Myeloid Differentiation Factor 88 / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • Toll-Like Receptor 4 / biosynthesis*
  • Toll-Like Receptor 4 / genetics
  • Transcription Factor RelA / biosynthesis*
  • Transcription Factor RelA / genetics
  • Vitamin D / therapeutic use*

Substances

  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • RNA, Messenger
  • Rela protein, rat
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Vitamin D
  • Streptozocin
  • Collagen
  • Glucose