title: Expression of PARK7 is increased in celiac disease.
abstract: Recently, it has been suggested that the gene called Parkinson's disease 7 (PARK7) might be an upstream activator of hypoxia-inducible factor (HIF)-1α, which plays a major role in sustaining intestinal barrier integrity. Furthermore, PARK7 has been proposed to participate in the Toll-like receptor (TLR)-dependent regulation of the innate immune system. Our aim was to investigate the involvement of PARK7 in the pathogenesis of coeliac disease (CD). Duodenal biopsy specimens were collected from 19 children with untreated CD, five children with treated CD (maintained on gluten-free diet), and ten children with histologically normal duodenal biopsies. PARK7 mRNA expression and protein level were determined by real-time polymerase chain reaction (PCR) and Western blot, respectively. Localization of PARK7 was visualized by immunofluorescence staining. Protein level of PARK7 increased in the duodenal mucosa of children with untreated CD compared to children with treated CD or to control biopsies (p <0.03). We detected intensive PARK7 staining in the epithelial cells and lamina propria of the duodenal mucosa of children with untreated CD compared with that in control biopsies. Our finding that mucosal expression of PARK7 is increased suggests that PARK7 is involved in the pathogenesis of gastrointestinal diseases, notably CD. Our results suggest that PARK7 may alter processes mediated by HIF-1α and TLR4, which supports a role for PARK7 in the maintenance of epithelial barrier integrity, immune homeostasis, or apoptosis.
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Vörös
authors.forename: Erna
authors.initials: E
authors.lastname: Sziksz
authors.forename: Leonóra
authors.initials: L
authors.lastname: Himer
authors.forename: Anna
authors.initials: A
authors.lastname: Onody
authors.forename: Domonkos
authors.initials: D
authors.lastname: Pap
authors.forename: Klára
authors.initials: K
authors.lastname: Frivolt
authors.forename: Beáta
authors.initials: B
authors.lastname: Szebeni
authors.forename: Rita
authors.initials: R
authors.lastname: Lippai
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Győrffy
authors.forename: Andrea
authors.initials: A
authors.lastname: Fekete
authors.forename: Ferenc
authors.initials: F
authors.lastname: Brandt
authors.forename: Kriszta
authors.initials: K
authors.lastname: Molnár
authors.forename: Gábor
authors.initials: G
authors.lastname: Veres
authors.forename: András
authors.initials: A
authors.lastname: Arató
authors.forename: Tivadar
authors.initials: T
authors.lastname: Tulassay
authors.forename: Adám
authors.initials: A
authors.lastname: Vannay
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D002446:Celiac Disease / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D055050:Diet, Gluten-Free; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D015513:Oncogene Proteins / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D012333:RNA, Messenger / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D015415:Biomarkers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1