Increased NOX1 and DUOX2 expression in the colonic mucosa of patients with chronic functional constipation

Medicine (Baltimore). 2022 Aug 12;101(32):e30028. doi: 10.1097/MD.0000000000030028.

Abstract

To determine whether oxidative stress and inflammation are associated with constipation by examining the expression of the main producers of reactive oxygen species, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and pro-inflammatory cytokines in the colon of patients with chronic functional constipation. The colonic biopsies were collected from 32 patients with chronic functional constipation and 30 healthy subjects who underwent colonoscopy. Colonic mucosal histology was observed. Interleukin (IL)-1β, IL-6, IL-8 messenger RNA (mRNA), and 4 members of NADPH oxidase (NOX1, NOX2, DUOX2, and NOX4) protein and mRNA were assessed by immunohistochemistry, western blotting, and reverse transcription polymerase chain reaction. The tissues from both patients and healthy subjects showed normal histological structure without increase of inflammatory cells. NOX1 protein and mRNA levels were significantly increased compared to controls (P < .05). DUOX2 protein, but not mRNA, was increased by 2-fold compared to controls (P < .05). The levels of NOX2 and NOX4 protein and mRNA demonstrated no significant difference between patients and control subjects. The levels of IL-1β and IL-6 mRNA were significantly higher in constipation patients (P < .05), while IL-8 mRNA level was no different between the 2 groups. NADPH oxidase and pro-inflammatory cytokine might be involved in the pathogeneses of chronic functional constipation.

MeSH terms

  • Colon / metabolism
  • Constipation / metabolism
  • Cytokines / metabolism
  • Dual Oxidases / genetics
  • Dual Oxidases / metabolism
  • Humans
  • Interleukin-6* / metabolism
  • Interleukin-8* / metabolism
  • Mucous Membrane
  • NADPH Oxidase 1 / metabolism*
  • NADPH Oxidase 4 / metabolism
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Cytokines
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Reactive Oxygen Species
  • Dual Oxidases
  • NADPH Oxidase 1
  • NADPH Oxidase 4
  • NADPH Oxidases
  • NOX1 protein, human
  • DUOX2 protein, human