The mineralocorticoid receptor-p38MAPK-NFB or ERK-Sp1 signal pathways mediate aldosterone-stimulated inflammatory and profibrotic responses in rat vascular smooth muscle cells

Chuan Jiang Zhu, Qing Qing Wang, Jun Lan Zhou, Han Zhi Liu, Fang Hua, Hong Zheng Yang, Zhuo Wei Hu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Aim:To explore the signalling pathways involved in aldosterone-induced inflammation and fibrosis in rat vascular smooth muscle cells (VSMCs).Methods:Using Western blotting and real-time RT-PCR, we investigated the effects of aldosterone on the expression of cyclooxygenase-2 (Cox-2) and IL-6, two important proinflammatory factors, and TGFΒ1, a critical profibrotic factor, in VSMCs.Results:Aldosterone treatment significantly increased the expression of Cox-2 and IL-6 and activation of p38MAPK and NF-B. The expression of both Cox-2 and IL-6 could be blocked by the mineralocorticoid receptor (MR) antagonist spironolactone and the p38MAPK inhibitor SB203580. Also, the rapid phosphorylation of p38MAPK could be suppressed by SB203580 but not by spironolactone, implicating in nongenomic effects of aldosterone. Similar to SB203580 and spironolactone, the NF-B inhibitor α-p-tosyl-L-lysine chloromethyl ketone (TLCK) markedly attenuated expression of Cox-2, indicating that MR, p38MAPK and NF-B are associated with aldosterone-induced inflammatory responses. Furthermore, aldosterone enhanced expression of TGFΒ1 in rat VSMCs. This result may be related to activation of the MR/ERK-Sp1 signalling pathway because PD98059, an ERK1/2 inhibitor, significantly blocked the rapid phosphorylation of ERK1/2 and function of Sp1 and led to reduced expression of TGFΒ1. Spironolactone was also shown to significantly inhibit TGFΒ1 and Sp1 expression but not ERK1/2 phosphorylation.Conclusion:These results suggest that aldosterone-induced inflammatory responses and fibrotic responses may be mediated by the MR/p38MAPK-NF-B pathways and the MR/ERK-Sp1 pathways in VSMCs, respectively.

Original languageEnglish (US)
Pages (from-to)873-878
Number of pages6
JournalActa Pharmacologica Sinica
Volume33
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • ERK1/2
  • NF-B
  • Sp1
  • aldosterone
  • fibrosis
  • inflammation
  • mineralocorticoid receptor
  • nongenomic effect
  • p38MAPK
  • signal transduction
  • vascular smooth muscle cells

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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