Differential activation of the STAT pathway by angiotensin II via angiotensin type 1 and type 2 receptors in cultured human fetal mesangial cells

Frank A. Seebach, Thomas Welte, Xin Yuan Fu, Lutz Henning Block, Michael Kashgarian

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The vasoactive peptide angiotensin II is the principal effector of the renin-angiotensin system. It exerts mitogenic and growth-inhibiting effects in many target tissues, including renal mesangial cells. To investigate mechanisms of angiotensin II signaling in human mesangial cells, we explored the signal transducer and activator of transcription (STAT) pathway as a possible regulator of angiotensin II receptor-specific signaling, We tested whether angiotensin II could induce STAT activation and nuclear translocation of STAT proteins in human mesangial cells by electromobility shift assays and by immunostaining and confocal microscopy. We found that fetal human mesangial cells express STAT 1,2,3,5, and 6 and that stimulation of these cells by angiotensin II results in rapid induction of STAT1 and STAT5 DNA-binding activity. This DNA-binding activity was identified as STAT5 for angiotensin receptor type 1 activation and STAT1 for angiotensin receptor type 2-mediated activation, as induction of STAT-DNA binding by angiotensin II could be differentially blocked by the angiotensin receptor type 1 blocker losartan and by angiotensin II receptor type 2 blocker PD 123,319. Angiotensin II also induced STAT1 and STAT5 tyrosine phosphorylation and nuclear translocation of activated STATs in a receptor subtype-specific manner. STAT activation thus appears to provide an important signaling pathway for angiotensin II-induced cellular responses.

Original languageEnglish (US)
Pages (from-to)265-273
Number of pages9
JournalExperimental and Molecular Pathology
Volume70
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Angiotensin Type 1 Receptor
Mesangial Cells
Angiotensins
Transcription
Transducers
Angiotensin II
Chemical activation
Transcriptional Activation
STAT2 Transcription Factor
DNA
Angiotensin II Type 2 Receptor Blockers
STAT Transcription Factors
Angiotensin Type 2 Receptor
STAT1 Transcription Factor
Angiotensin II Type 1 Receptor Blockers
Phosphorylation
Angiotensin Receptors
Losartan
Confocal microscopy
Renin-Angiotensin System

Keywords

  • Activators of transcription
  • Angiotensin II
  • Angiotensin receptors
  • Hypertension
  • Signal transducers
  • Transcription factors

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

Cite this

Differential activation of the STAT pathway by angiotensin II via angiotensin type 1 and type 2 receptors in cultured human fetal mesangial cells. / Seebach, Frank A.; Welte, Thomas; Fu, Xin Yuan; Block, Lutz Henning; Kashgarian, Michael.

In: Experimental and Molecular Pathology, Vol. 70, No. 3, 2001, p. 265-273.

Research output: Contribution to journalArticle

Seebach, Frank A. ; Welte, Thomas ; Fu, Xin Yuan ; Block, Lutz Henning ; Kashgarian, Michael. / Differential activation of the STAT pathway by angiotensin II via angiotensin type 1 and type 2 receptors in cultured human fetal mesangial cells. In: Experimental and Molecular Pathology. 2001 ; Vol. 70, No. 3. pp. 265-273.
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