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SGK1-dependent upregulation of connective tissue growth factor by angiotensin II

Azeemudeen Hussain1, Amanda W Wyatt, Kan Wang

  • 1Department of Physiology, University of Tübingen,Tübingen, Germany.

Kidney & Blood Pressure Research
|March 6, 2008
PubMed

Insights

Angiotensin II stimulates serum- and glucocorticoid-inducible kinase (SGK1) expression, which is essential for angiotensin II-induced connective tissue growth factor (CTGF) production, suggesting SGK1

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Physiology

Background:

  • Angiotensin II is known to induce fibrosis, a process involving connective tissue growth factor (CTGF).
  • The precise signaling pathways connecting angiotensin II to CTGF production remain unclear.
  • Serum- and glucocorticoid-inducible kinase 1 (SGK1) is highly expressed in fibrotic tissues.

Purpose of the Study:

  • To investigate if angiotensin II transcriptionally regulates SGK1.
  • To determine if SGK1 plays a role in the angiotensin II-mediated regulation of CTGF expression.

Main Methods:

  • Experiments were conducted using human kidney fibroblasts and mouse lung fibroblasts.
  • Fibroblasts were derived from gene-targeted mice lacking SGK1 (sgk1-/-) and their wild-type littermates (sgk1+/+).
  • Measurements included SGK1 and CTGF protein and transcript levels following angiotensin II treatment.

Main Results:

  • Angiotensin II increased both SGK1 and CTGF protein expression in human renal fibroblasts within 4 hours.
  • In wild-type mouse fibroblasts, angiotensin II significantly upregulated SGK1 transcript levels after 4 hours.
  • Angiotensin II stimulated CTGF expression in wild-type fibroblasts, but this effect was significantly reduced in SGK1-deficient fibroblasts.

Conclusions:

  • Angiotensin II stimulates SGK1 expression.
  • SGK1 is required for angiotensin II to stimulate CTGF expression.
  • SGK1 likely contributes to the profibrotic actions of angiotensin II.

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