title: AT1 antagonist modulates activin-like kinase 5 and TGF-beta receptor II in the developing kidney.
abstract: Previous studies by our group have demonstrated that angiotensin-converting enzyme (ACE) inhibition in the developing kidney modulates transforming growth factor-beta receptors. Blocking of angiotensin II (ANG II) mainly through angiotensin II type 1 receptor (AT1) has been implicated in mediating this ACE inhibition. The present study was designed to investigate the effects of an AT1 antagonist, losartan, on transforming growth factor-beta1 (TGF-beta1), TGF-beta receptor I [TbetaRI, activin-like kinase (ALK)-1, ALK-5], TGF-beta receptor II (TbetaRII), and alpha-smooth muscle actin (alpha-SMA) expression in the developing kidney. Newborn rat pups were treated with losartan (30 mg/kg per day) or normal saline for 7 days. Kidneys were removed for immunohistochemistry, reverse transcription polymerase chain reaction (PCR), and Western blotting of TGF-beta1, ALK-1, ALK-5, TbetaRII, and alpha-SMA. Renal ALK-5 and TbetaRII protein expressions in the losartan-treated group were found to be significantly increased (P<0.05), whereas TGF-beta1, ALK-1, and alpha-SMA protein expressions were not changed by losartan treatment. The losartan-treated group also showed significantly increased mean tubular diameter and interstitial area of the kidney (P<0.05). These results suggest that AT1 inhibition in the developing kidney impairs renal growth and development and modulates the expression of ALK-5 and TbetaRII.
authors.affiliation: Department of Pediatrics, College of Medicine, Korea University, 152-703 Seoul, South Korea.
authors.forename: Hyung Eun
authors.initials: HE
authors.lastname: Yim
authors.forename: Mee Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: In Sun
authors.initials: IS
authors.lastname: Bae
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung Min
authors.initials: BM
authors.lastname: Choi
authors.forename: Kee Hwan
authors.initials: KH
authors.lastname: Yoo
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Hong
authors.forename: Joo Won
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D030201:Activin Receptors, Type I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000502:physiology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D030201:Activin Receptors, Type I; D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D019808:Losartan; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat; C000625843:Tgfbr1 protein, rat