title: Carnosic acid attenuates unilateral ureteral obstruction-induced kidney fibrosis via inhibition of Akt-mediated Nox4 expression.
abstract: Fibrosis represents a common pathway to end-stage renal disease. Transforming growth factor-β (TGF-β) plays a critical role in the progression of kidney fibrosis. In the present study, we explored the effect of carnosic acid (CA) against TGF-β-induced fibroblast activation in vitro and unilateral ureteral obstruction (UUO)-induced kidney fibrosis in vivo. CA attenuated TGF-β-induced up-regulation of profibrogenic proteins, α-smooth muscle actin (α-SMA), collagen I (COLI), fibronectin (FN), and plasminogen activator inhibitor-1 (PAI-1) in kidney fibroblast cells (NRK-49F). CA inhibited TGF-β-induced hydrogen peroxide generation via inhibition of NADPH oxidase 4 (Nox4) expressions. In mice, CA-administration markedly mitigated the UUO-induced interstitial extension, collagen deposition, superoxide anion formation, hydrogen peroxide production, and lipid peroxidation. In addition, CA significantly attenuated the expression of α-SMA, COLI, FN, PAI-1, and Nox4 in UUO-induced kidneys. These results indicated that CA attenuated oxidative stress via inhibition of Nox4 expression in TGF-β-stimulated fibroblasts and UUO operated-kidneys, suggesting that CA may be useful for the treatment of fibrosis-related diseases.
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Kyong-Jin
authors.initials: KJ
authors.lastname: Jung
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Min
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Anatomy, School of Medicine, Kyungpook National University, Taegu 700-422, Republic of Korea.
authors.forename: Kwon Moo
authors.initials: KM
authors.lastname: Park
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea. Electronic address: kwontk@dsmc.or.kr.
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D045784:Abietanes / Q000008:administration & dosage*; D000199:Actins / Q000235:genetics*; D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D051379:Mice; D000074663:NADPH Oxidase 4 / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014517:Ureteral Obstruction
chemical_list: D045784:Abietanes; D000199:Actins; D024042:Collagen Type I; D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse; D000074663:NADPH Oxidase 4; D051057:Proto-Oncogene Proteins c-akt; C018381:salvin
keywords: Akt; Carnosic acid; Kidney fibrosis; Nox4; Unilateral ureteral obstruction