SGK1-dependent upregulation of connective tissue growth factor by angiotensin II.
Angiotensin II has previously been shown to trigger fibrosis, an effect involving connective tissue growth factor (CTGF). The signaling pathways linking angiotensin II to CTGF formation are, however, incompletely understood. A gene highly expressed in fibrosing tissue is the serum- and glucocorticoid-inducible kinase SGK1. The present study explored whether SGK1 is transcriptionally regulated by angiotensin II and participates in the angiotensin II-dependent regulation of CTGF expression. To this end, experiments have been performed in human kidney fibroblasts and mouse lung fibroblasts from gene-targeted mice lacking SGK1 (sgk1-/-) and their wild-type littermates (sgk1+/+). In human renal fibroblasts, SGK1 and CTGF protein expression were enhanced by angiotensin II (10 nM) within 4 h. In sgk1+/+ mouse fibroblasts, SGK1 transcript levels were significantly increased after 4 h of angiotensin II treatment. Angiotensin II stimulated both transcript and protein abundance of CTGF in fibroblasts from sgk1+/+ mice, effects significantly blunted in fibroblasts of sgk1-/- mice. In conclusion, angiotensin II stimulates the expression of SGK1, which is in turn required for the stimulating effect of angiotensin II on the expression of CTGF. Thus, SGK1 presumably contributes to the profibrotic effect of angiotensin II.
Hussain
Azeemudeen
A
Department of Physiology, University of Tübingen,Tübingen, Germany.
Wyatt
Amanda W
AW
Wang
Kan
K
Bhandaru
Madhuri
M
Biswas
Raja
R
Avram
Diana
D
Föller
Michael
M
Rexhepaj
Rexhep
R
Friedrich
Björn
B
Ullrich
Susanne
S
Müller
Gerhard
G
Kuhl
Dietmar
D
Risler
Teut
T
Lang
Florian
F
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D055513:Connective Tissue Growth Factor; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D008168:Lung / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015854:Up-Regulation; D000099184:Serum-Glucocorticoid Regulated Kinases
D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C526317:CCN2 protein, human; C526318:CCN2 protein, mouse