Involvement of transforming growth factor-β in regulation of calcium transients in diabetic vascular smooth muscle cells

Kumar Sharma, Leo Deelman, Muniswamy Madesh, Bernd Kurz, Emilio Ciccone, Senthuran Siva, Taishan Hu, Yanqing Zhu, Lewei Wang, Robert Henning, Xinliang Ma, Gyorgy Hajnoczky

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Altered calcium [Ca2+] transients of vascular smooth muscle cells to vasoconstrictors may contribute to altered regulation of blood flow in diabetes. We postulated that diabetes-induced transforming growth factor (TGF)-β production contributes to impaired ANG II response of vascular smooth muscle cells in macrovessels and microvessels. Aortic vascular smooth muscle cells isolated from diabetic rats exhibited markedly impaired ANG II-induced cytosolic calcium [Ca2+] signal that was completely restored by pretreatment with anti-TGF-β antibodies. Similar findings were noted in microvascular smooth muscle cells isolated from preglomerular vessels and cultured in high glucose. The impact of diabetes on [Ca2+] transients was replicated by addition of TGF-β1 and -β2 isoforms to aortic smooth muscle cells in culture and diabetic cells had enhanced production of TGF-β2. In the in vivo condition, TGF-β1 was increased in diabetic glomeruli, whereas TGF-β2 was increased in diabetic aorta. The characteristic increase in glomerular filtration surface area found in diabetic rats was prevented by treatment with anti-TGF-β antibodies, and impaired ANG II-induced aortic ring contraction in diabetic rats was completely restored by anti-TGF-β antibodies. Impaired vascular dysfunction may be partly due to decreased inositol 1,4,5-trisphosphate receptor (IP3R), as reduced type I IP3R expression was found in diabetic aorta and restored by anti-TGF-β antibodies. We conclude that TGF-β plays an important role in the vascular dysfunction of early diabetes by inhibiting calcium transients in vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)F1258-F1270
JournalAmerican Journal of Physiology - Renal Physiology
Volume285
Issue number6 54-6
StatePublished - Dec 1 2003
Externally publishedYes

Keywords

  • Angiotensin II
  • Experimental diabetes
  • Glomerular hypertrophy
  • Inositol 1,4,5-trisphosphate receptor
  • Intracellular calcium
  • Microvessels

ASJC Scopus subject areas

  • Physiology
  • Urology

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