Balance of meprin A and B in mice affects the progression of experimental inflammatory bowel disease

Sanjita Banerjee, Ge Jin, S. Gaylen Bradley, Gail L. Matters, Ryan D. Gailey, Jacqueline M. Crisman, Judith S. Bond

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

MEP1A, which encodes the α subunit of meprin metalloproteinases, is a susceptibility gene for inflammatory bowel disease (IBD), and decreased intestinal meprin-α expression is associated with enhanced IBD in humans. Mice lacking meprin α (α knockout, αKO) have more severe colitis induced by dextran sulfate sodium (DSS) than wild-type (WT) mice, indicating an anti-inflammatory role for meprin A. Previous studies and those herein indicate the meprin B has proinflammatory activities. Therefore, mice lacking both meprin A and B (dKO mice) were generated to determine how their combined absence alters the inflammatory response to DSS. Unchallenged dKO mice grow and reproduce normally and have no obvious abnormal phenotype, except for a slightly elevated plasma albumin in both males and females and a lower urine creatinine level in dKO males. Upon oral administration of 3.5% DSS, the dKO mice have more severe colitis than the WT and βKO mice but significantly less than the αKO mice. The dKO mice lose more weight and have elevated MPO and IL-6 activities in the colon compared with WT mice. Systemic inflammation, monitored by plasma nitric oxide levels, is absent in DSS-treated dKO mice, unlike WT mice. The severity of experimental IBD in dKO mice is intermediate between αKO and WT mice. The data indicate that the absence of meprin A aggravates chronic inflammation and the lack of meprin B affords some protection from injury. Manipulation of the expression of meprin gene products may have therapeutic potential.

Original languageEnglish (US)
Pages (from-to)G273-G282
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume300
Issue number2
DOIs
StatePublished - Feb 2011

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Balance of meprin A and B in mice affects the progression of experimental inflammatory bowel disease'. Together they form a unique fingerprint.

Cite this