MMP9 is involved in HO-1-mediated upregulation of apical junctional complex in Caco-2 cells under oxygen-glucose deprivation

Biochem Biophys Res Commun. 2018 Mar 25;498(1):125-131. doi: 10.1016/j.bbrc.2018.02.045. Epub 2018 Feb 6.

Abstract

Ischemia reperfusion injury is a critical factor in the recovery process after intestine trauma and the functional restoration of intestinal reconstruction. This study was the first to explore the expression of apical junctional complex (AJC) induced by heme oxygenase-1 (HO-1) in Caco-2 cells in oxygen-glucose deprivation (OGD) models. Here we showed that HO-1 was upregulated after OGD. Notably, activation of HO-1 largely enhanced the expression of AJC proteins including Claudin-4, E-cadherin and β-catenin in Caco-2 cells, but decreased the expression of matrix metalloproteinase 9 (MMP9). Knockdown of HO-1 attenuated the OGD-induced overexpression of AJC proteins but promoted the expression of MMP9. Interestingly, inhibition of MMP9 further enhanced AJC expression. These results suggest that HO-1 is involved in OGD-evoked upregulation of AJC proteins, which is partly mediated by MMP9 pathway. High expression of HO-1 may play an important role in the pathophysiological process of ischemia reperfusion injury and has potential clinical value for the treatment of intestine related diseases.

Keywords: Apical junctional complex; Heme oxygenase-1; Ischemia reperfusion injury; Matrix metalloproteinase 9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Caco-2 Cells
  • Cadherins / metabolism
  • Claudin-4 / metabolism
  • Gene Knockdown Techniques
  • Gene Silencing / drug effects
  • Glucose / deficiency*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Intercellular Junctions / drug effects
  • Intercellular Junctions / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Models, Biological
  • Oxygen / metabolism*
  • Up-Regulation* / drug effects
  • beta Catenin / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Claudin-4
  • Matrix Metalloproteinase Inhibitors
  • beta Catenin
  • Heme Oxygenase-1
  • Matrix Metalloproteinase 9
  • Glucose
  • Oxygen