title: Microarray Analysis Reveals Increased Expression of Matrix Metalloproteases and Cytokines of Interleukin-20 Subfamily in the Kidneys of Neonate Rats Underwent Unilateral Ureteral Obstruction: A Potential Role of IL-24 in the Regulation of Inflammation and Tissue Remodeling.
abstract: Congenital obstructive nephropathy (CON) is the main cause of pediatric chronic kidney diseases leading to renal fibrosis. High morbidity and limited treatment opportunities of CON urge the better understanding of the underlying molecular mechanisms.
  
  
  
  To identify the differentially expressed genes, microarray analysis was performed on the kidney samples of neonatal rats underwent unilateral ureteral obstruction (UUO). Microarray results were then validated by real-time RT-PCR and bioinformatics analysis was carried out to identify the relevant genes, functional groups and pathways involved in the pathomechanism of CON. Renal expression of matrix metalloproteinase (MMP)-12 and interleukin (IL)-24 were evaluated by real-time RT-PCR, flow cytometry and immunohistochemical analysis. Effect of the main profibrotic factors on the expression of MMP-12 and IL-24 was investigated on HK-2 and HEK-293 cell lines. Finally, the effect of IL-24 treatment on the expression of pro-inflammatory cytokines and MMPs were tested in vitro.
  
  
  
  Microarray analysis revealed 880 transcripts showing >2.0-fold change following UUO, enriched mainly in immune response related processes. The most up-regulated genes were MMPs and members of IL-20 cytokine subfamily, including MMP-3, MMP-7, MMP-12, IL-19 and IL-24. We found that while TGF-β treatment inhibits the expression of MMP-12 and IL-24, H2O2 or PDGF-B treatment induce the epithelial expression of MMP-12. We demonstrated that IL-24 treatment decreases the expression of IL-6 and MMP-3 in the renal epithelial cells.
  
  
  
  This study provides an extensive view of UUO induced changes in the gene expression profile of the developing kidney and describes novel molecules, which may play significant role in the pathomechanism of CON.
authors.affiliation: MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.|1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Domonkos
authors.initials: D
authors.lastname: Pap
authors.affiliation: MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.|1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Erna
authors.initials: E
authors.lastname: Sziksz
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kiss
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Réka
authors.initials: R
authors.lastname: Rokonay
authors.affiliation: MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.|1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Apor
authors.initials: A
authors.lastname: Veres-Székely
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Lippai
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: István Márton
authors.initials: IM
authors.lastname: Takács
authors.affiliation: MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Kis
authors.affiliation: MTA-SE, Lendület Diabetes Research Group, Budapest, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fekete
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Reusz
authors.affiliation: MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.|1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Attila J
authors.initials: AJ
authors.lastname: Szabó
authors.affiliation: MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.|1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Adam
authors.initials: A
authors.lastname: Vannay
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019295:Computational Biology / Q000379:methods; D016207:Cytokines / Q000378:metabolism*; D020869:Gene Expression Profiling; D007249:Inflammation / Q000517:prevention & control; D007378:Interleukins / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D007668:Kidney / Q000378:metabolism*; D053508:Matrix Metalloproteinase 12 / Q000032:analysis; D008666:Metalloendopeptidases / Q000378:metabolism*; D046228:Microarray Analysis / Q000379:methods; D051381:Rats; D012038:Regeneration / Q000187:drug effects; D014517:Ureteral Obstruction / Q000151:congenital / Q000378:metabolism*; D000099180:Interleukin-24
chemical_list: D016207:Cytokines; D007378:Interleukins; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases; D000099180:Interleukin-24; C000602030:matrix metallopeptidase 12, rat; C422042:interleukin 20
keywords: CKD; Congenital obstructive nephropathy; MMP-12, IL-24; Microarray; Newborn; Unilateral ureteral obstruction