Aldosterone-induced inflammatory response of mesangial cells via angiotension II receptors

J Renin Angiotensin Aldosterone Syst. 2015 Dec;16(4):739-48. doi: 10.1177/1470320313519486. Epub 2014 Jan 24.

Abstract

Introduction: In this study, we investigated whether AngII receptors (AT1a and AT2) contributed to the development of the aldosterone-induced inflammatory response of rat mesangial cells (RMCs).

Materials and methods: RMCs were isolated from the glomeruli of normal or diabetic rats which were produced by injection of streptozotocin, and cultured in high-glucose media. In order to evaluate the effects of aldosterone, the expression of AT1a, AT2, NF-κB and MCP-1 was detected. In addition, in order to evaluate the role of Ang II receptors, AT1a and AT2 genes were blocked and the expression of NF-κB and MCP-1 was detected. Moreover, for assessing the relationship between NF-κB and MCP-1, the NF-κB gene was blocked and MCP-1 expression was detected.

Results: Aldosterone significantly increased AT1a, AT2, NF-κB and MCP-1 levels in RMCs in a dose-dependent manner, whereas eplerenone (EPI), a selective aldosterone antagonist, partly inhibited the effects of aldosterone. When AT1a and AT2 genes were blocked, the expression of NF-κB and MCP-1 was greatly inhibited. Moreover, when the NF-κB gene was silenced, the expression of MCP-1 was reduced.

Conclusion: We demonstrated that aldosterone induced an inflammatory response in RMCs cultured in high-glucose media via the AT1a and AT2 pathways.

Keywords: AT1a; AT2; Aldosterone; MCP-1; NF-κB; inflammatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / adverse effects*
  • Animals
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Dexamethasone / pharmacology
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Gene Knockdown Techniques
  • Inflammation / genetics
  • Inflammation / pathology
  • Male
  • Mesangial Cells / drug effects
  • Mesangial Cells / metabolism*
  • Mesangial Cells / pathology*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Receptor, Angiotensin, Type 2 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism*
  • Receptors, Mineralocorticoid / genetics
  • Receptors, Mineralocorticoid / metabolism

Substances

  • Ccl2 protein, rat
  • Chemokine CCL2
  • NF-kappa B
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Mineralocorticoid
  • Aldosterone
  • Dexamethasone