title: DJ-1 regulates the expression of renal (pro)renin receptor via reactive oxygen species-mediated epigenetic modification.
abstract: BACKGROUND
  DJ-1 protein plays multifunctional roles including transcriptional regulation and scavenging oxidative stress; thus, it may be associated with the development of renal disorders. We investigated whether DJ-1 protein regulates the expression of (pro)renin receptor (PRR), a newly identified member of renin-angiotensin system.
  
  
  METHODS
  The levels of mRNA and protein were determined by real-time PCR and western blot, respectively. H2O2 production was tested by using fluorescence probe. Histone modification was determined by chromatin immunoprecipitation.
  
  
  RESULTS
  The expression of PRR was significantly higher in the kidney from DJ-1 knockout mice (DJ-1-/-) compared with wild-type mice (DJ-1+/+). Histone deacetylase 1 recruitment at the PRR promoter was lower, and histone H3 acetylation and RNA polymerase II recruitment were higher in DJ-1-/- than in DJ-1+/+. Knockdown or inhibition of histone deacetylase 1 restored PRR expression in mesangial cells from DJ-1+/+. H2O2 production was greater in DJ-1-/- cells compared with DJ-1+/+ cells. These changes in PRR expression and epigenetic modification in DJ-1-/- cells were induced by H2O2 treatment and reversed completely by addition of an antioxidant reagent. Prorenin-stimulated ERK1/2 phosphorylation was greater in DJ-1-/- than in DJ-1+/+ cells and this was inhibited by a PRR-inhibitory peptide, and by AT1 and AT2 receptor inhibitors. The expression of renal fibrotic genes was higher in DJ-1-/- than in DJ-1+/+ cells and decreased in PRR-knockdown DJ-1-/- cells.
  
  
  CONCLUSIONS
  We conclude that DJ-1 protein regulates the expression of renal PRR through H2O2-mediated epigenetic modification.
  
  
  CONCLUSIONS
  We suggest that renal DJ-1 protein may be an important molecule in the acceleration of renal pathogenesis through PRR regulation.
authors.affiliation: Department of Physiology, Functional Genomics Institute, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, Republic of Korea.
authors.forename: Dong-Youb
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Immunology, Functional Genomics Institute, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, Republic of Korea.
authors.forename: Hyuk Soon
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Physiology, Functional Genomics Institute, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, Republic of Korea.
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Won
authors.affiliation: Department of Physiology, Functional Genomics Institute, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, Republic of Korea.
authors.forename: Kang Pa
authors.initials: KP
authors.lastname: Lee
authors.affiliation: Department of Physiology, Functional Genomics Institute, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, Republic of Korea.
authors.forename: Seung Hyo
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Physiology, Functional Genomics Institute, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, Republic of Korea.
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.affiliation: Department of Immunology, Functional Genomics Institute, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, Republic of Korea.
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Department of Herbal Cosmetic Science, College of Natural Science, Hoseo University, Asan 336-795, Republic of Korea.
authors.forename: Hwan Myung
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Physiology, Functional Genomics Institute, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, Republic of Korea. Electronic address: bkkim2@kku.ac.kr.
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D044127:Epigenesis, Genetic; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D054464:Peroxiredoxins; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic; D000071617:Protein Deglycase DJ-1; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D000093342:Prorenin Receptor
chemical_list: D006657:Histones; D015513:Oncogene Proteins; D016877:Oxidants; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011956:Receptors, Cell Surface; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D048052:Mitogen-Activated Protein Kinase 3; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D000093342:Prorenin Receptor
keywords: (Pro)Renin receptor; DJ-1; Epigenetic modification; Oxidative stress