title: SGK1-dependent upregulation of connective tissue growth factor by angiotensin II.
abstract: 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.
authors.affiliation: Department of Physiology, University of Tübingen,Tübingen, Germany.
authors.forename: Azeemudeen
authors.initials: A
authors.lastname: Hussain
authors.forename: Amanda W
authors.initials: AW
authors.lastname: Wyatt
authors.forename: Kan
authors.initials: K
authors.lastname: Wang
authors.forename: Madhuri
authors.initials: M
authors.lastname: Bhandaru
authors.forename: Raja
authors.initials: R
authors.lastname: Biswas
authors.forename: Diana
authors.initials: D
authors.lastname: Avram
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Rexhep
authors.initials: R
authors.lastname: Rexhepaj
authors.forename: Björn
authors.initials: B
authors.lastname: Friedrich
authors.forename: Susanne
authors.initials: S
authors.lastname: Ullrich
authors.forename: Gerhard
authors.initials: G
authors.lastname: Müller
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.forename: Teut
authors.initials: T
authors.lastname: Risler
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: 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
chemical_list: 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