Role of microRNA-223 in the regulation of poly(ADP-ribose) polymerase in pediatric patients with Crohn’s disease

Nóra Judit Béres, Zoltán Kiss, Katalin E. Müller, Áron Cseh, Apor Veres-Székely, Rita Lippai, Rita Benkő, Árpád Bartha, Szabolcs Heininger, A. Vannay, Erna Sziksz, Gábor Veres, Eszter M. Horváth

Research output: Contribution to journalArticle

Abstract

Objectives: Crohn’s disease (CD) is a multifactorial disease, characterized by oxidant-induced tissue injury with a possible activation of poly(ADP-ribose) polymerase (PARP)-1. MicroRNAs (miRs) can offer a potential link between the genetic susceptibility, environmental and immunologic factors in the pathogenesis of CD. Previously, PARP-1 was identified as a direct target gene of miR-223 in an epithelial cell line. Our aim was to examine PARP activation and miR-223 expression in colonic biopsies of pediatric CD. To support our in vivo findings, the effect of lipopolysaccharide (LPS) on same parameters was examined in HT-29 colonic epithelial cell line. Methods: Colonic biopsies were taken from patients with macroscopically inflamed and intact mucosa with CD and controls. LPS treated HT-29 cells served as our in vitro model. To analyze the PARP-1 expression real-time PCR, Western blot and immunohistochemical analyses were used. PARP-1 enzymatic activity was assessed on the basis of poly(ADP-ribosyl)ated proteins. Expression of miR-223 was examined by real-time PCR. Results: PARP-1 mRNA and miR-223 expression was significantly elevated, however, the amount of PARP-1 protein and poly(ADP-ribose) was reduced in pediatric CD compared to controls. LPS incubation did not affect the expression of PARP-1 mRNA, however, decreased miR-223 expression, and enhanced PARP-1 activity. Conclusions: In our study, we showed that the expression of miR-223 is up-regulated and poly(ADP-ribosyl)ation is reduced in pediatric patients with CD. Moreover, we confirmed their opposite change in LPS treated epithelial cells, too. These data suggest that the hypofunctionality of PARP-1 may play a potential role in the pathomechanism of CD.

Original languageEnglish
JournalScandinavian Journal of Gastroenterology
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Poly(ADP-ribose) Polymerases
MicroRNAs
Crohn Disease
Pediatrics
Lipopolysaccharides
Epithelial Cells
Real-Time Polymerase Chain Reaction
Poly Adenosine Diphosphate Ribose
Biopsy
Poly (ADP-Ribose) Polymerase-1
Cell Line
HT29 Cells
Messenger RNA
Immunologic Factors
Genetic Predisposition to Disease
Oxidants
Adenosine Diphosphate
Mucous Membrane
Western Blotting
Wounds and Injuries

Keywords

  • Crohn’s disease
  • miR-223
  • pediatric
  • Poly(ADP-ribose)
  • poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Role of microRNA-223 in the regulation of poly(ADP-ribose) polymerase in pediatric patients with Crohn’s disease. / Judit Béres, Nóra; Kiss, Zoltán; Müller, Katalin E.; Cseh, Áron; Veres-Székely, Apor; Lippai, Rita; Benkő, Rita; Bartha, Árpád; Heininger, Szabolcs; Vannay, A.; Sziksz, Erna; Veres, Gábor; Horváth, Eszter M.

In: Scandinavian Journal of Gastroenterology, 01.01.2018.

Research output: Contribution to journalArticle

Judit Béres, N, Kiss, Z, Müller, KE, Cseh, Á, Veres-Székely, A, Lippai, R, Benkő, R, Bartha, Á, Heininger, S, Vannay, A, Sziksz, E, Veres, G & Horváth, EM 2018, 'Role of microRNA-223 in the regulation of poly(ADP-ribose) polymerase in pediatric patients with Crohn’s disease', Scandinavian Journal of Gastroenterology. https://doi.org/10.1080/00365521.2018.1498915
Judit Béres, Nóra ; Kiss, Zoltán ; Müller, Katalin E. ; Cseh, Áron ; Veres-Székely, Apor ; Lippai, Rita ; Benkő, Rita ; Bartha, Árpád ; Heininger, Szabolcs ; Vannay, A. ; Sziksz, Erna ; Veres, Gábor ; Horváth, Eszter M. / Role of microRNA-223 in the regulation of poly(ADP-ribose) polymerase in pediatric patients with Crohn’s disease. In: Scandinavian Journal of Gastroenterology. 2018.
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abstract = "Objectives: Crohn’s disease (CD) is a multifactorial disease, characterized by oxidant-induced tissue injury with a possible activation of poly(ADP-ribose) polymerase (PARP)-1. MicroRNAs (miRs) can offer a potential link between the genetic susceptibility, environmental and immunologic factors in the pathogenesis of CD. Previously, PARP-1 was identified as a direct target gene of miR-223 in an epithelial cell line. Our aim was to examine PARP activation and miR-223 expression in colonic biopsies of pediatric CD. To support our in vivo findings, the effect of lipopolysaccharide (LPS) on same parameters was examined in HT-29 colonic epithelial cell line. Methods: Colonic biopsies were taken from patients with macroscopically inflamed and intact mucosa with CD and controls. LPS treated HT-29 cells served as our in vitro model. To analyze the PARP-1 expression real-time PCR, Western blot and immunohistochemical analyses were used. PARP-1 enzymatic activity was assessed on the basis of poly(ADP-ribosyl)ated proteins. Expression of miR-223 was examined by real-time PCR. Results: PARP-1 mRNA and miR-223 expression was significantly elevated, however, the amount of PARP-1 protein and poly(ADP-ribose) was reduced in pediatric CD compared to controls. LPS incubation did not affect the expression of PARP-1 mRNA, however, decreased miR-223 expression, and enhanced PARP-1 activity. Conclusions: In our study, we showed that the expression of miR-223 is up-regulated and poly(ADP-ribosyl)ation is reduced in pediatric patients with CD. Moreover, we confirmed their opposite change in LPS treated epithelial cells, too. These data suggest that the hypofunctionality of PARP-1 may play a potential role in the pathomechanism of CD.",
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AU - Judit Béres, Nóra

AU - Kiss, Zoltán

AU - Müller, Katalin E.

AU - Cseh, Áron

AU - Veres-Székely, Apor

AU - Lippai, Rita

AU - Benkő, Rita

AU - Bartha, Árpád

AU - Heininger, Szabolcs

AU - Vannay, A.

AU - Sziksz, Erna

AU - Veres, Gábor

AU - Horváth, Eszter M.

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