title: Role of AMP-activated protein kinase α1 in angiotensin-II-induced renal Tgfß-activated kinase 1 activation.
abstract: Angiotensin-II is a key factor in renal fibrosis. Obstructive nephropathy induces an isoform shift from catalytic Ampkα2 towards Ampkα1 which contributes to signaling involved in renal tissue injury. The present study explored whether the Ampkα1 isoform contributes to the renal effects of angiotensin-II. To this end, angiotensin-II was infused by subcutaneous implantation of osmotic minipumps in gene-targeted mice lacking functional Ampkα1 (Ampkα1(-/-)) and corresponding wild-type mice (Ampkα1(+/+)). Western blotting and qRT-PCR were employed to determine protein abundance and mRNA levels, respectively, in renal tissue. In Ampkα1(+/+) mice, angiotensin-II increased renal Ampkα1 protein expression without significantly modifying renal Ampkα2 protein expression. The renal phosphorylated Ampkα (Thr(172)) protein abundance was not affected by angiotensin-II in neither genotypes, but was significantly lower in Ampkα1(-/-) mice than Ampkα1(+/+) mice. Angiotensin-II increased the phosphorylation of Tak1 (Ser(412)) in renal tissue of Ampkα1(+/+) mice, an effect virtually absent in the Ampkα1(-/-) mice. Furthermore, angiotensin-II treatment significantly increased renal protein and mRNA expression of α-smooth muscle actin (αSma) as well as Tak1-target gene expression: Cox2, Il6 and Pai1 in Ampkα1(+/+) mice, all effects significantly less pronounced in Ampkα1(-/-) mice. In conclusion, angiotensin-II up-regulates the Ampkα1 isoform in renal tissue. Ampkα1 participates in renal Tak1 activation and Tak1-dependent signaling induced by angiotensin-II.
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, D-72076 Tuebingen, Germany; Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, D-72076 Tuebingen, Germany.
authors.forename: Sobuj
authors.initials: S
authors.lastname: Mia
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, D-72076 Tuebingen, Germany; Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, D-72076 Tuebingen, Germany.
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Castor
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, D-72076 Tuebingen, Germany; Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, D-72076 Tuebingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Musculus
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, D-72076 Tuebingen, Germany; Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, D-72076 Tuebingen, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Voelkl
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, D-72076 Tuebingen, Germany; Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, D-72076 Tuebingen, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, D-72076 Tuebingen, Germany; Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, D-72076 Tuebingen, Germany. Electronic address: florian.lang@uni-tuebingen.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000199:Actins / Q000235:genetics; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics; D004789:Enzyme Activation; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000235:genetics; D007668:Kidney / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D055372:AMP-Activated Protein Kinases; D000199:Actins; D000804:Angiotensin II; D051546:Cyclooxygenase 2; D015850:Interleukin-6; D020930:MAP Kinase Kinase Kinases; D012333:RNA, Messenger; D000099151:MAP Kinase Kinase Kinase 7; C544013:alpha-smooth muscle actin, mouse; C577686:interleukin-6, mouse; C077623:Ptgs2 protein, mouse; C548179:Prkaa1 protein, mouse
keywords: Ampkα1; Angiotensin-II; Renal inflammation; Tgfß-activated kinase 1; αSma