Role of microRNA-223 in the regulation of poly(ADP-ribose) polymerase in pediatric patients with Crohn’s disease
| Autor: | Gábor Veres, Nóra Judit Béres, Áron Cseh, Katalin Eszter Müller, Rita Benkő, Eszter M. Horváth, Árpád Bartha, Apor Veres-Székely, Rita Lippai, Szabolcs Heininger, Erna Sziksz, Ádám Vannay, Zoltán Kiss |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Adolescent Poly ADP ribose polymerase Blotting Western Poly (ADP-Ribose) Polymerase-1 Klinikai orvostudományok Pathogenesis 03 medical and health sciences Crohn Disease Western blot mir-223 In vivo microRNA Humans Medicine Child Cells Cultured Polymerase biology medicine.diagnostic_test business.industry Gastroenterology Epithelial Cells Orvostudományok Up-Regulation MicroRNAs 030104 developmental biology Child Preschool Linear Models biology.protein Cancer research Immunohistochemistry business HT29 Cells |
| Zdroj: | Scandinavian Journal of Gastroenterology. 53:1066-1073 |
| ISSN: | 1502-7708 0036-5521 |
| DOI: | 10.1080/00365521.2018.1498915 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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