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Activities of matrix metalloproteinase-2, matrix metalloproteinase-9, and serine proteases in samples of the colorectal mucosa of Miniature Dachshunds with inflammatory colorectal polyps

Noriyuki Nagata DVM1, Hiroshi Ohta DVM, PhD1, Arisa Yamada DVM1, Yong Bin Teoh DVM1, Osamu Ichii DVM, PhD2, Keitaro Morishita DVM, PhD3, Noboru Sasaki DVM, PhD1, and Mitsuyoshi Takiguchi DVM, PhD1
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  • 1 1Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Sapporo 060-0818.
  • | 2 2Department of Veterinary Clinical Sciences; Laboratory of Anatomy, Department of Basic Veterinary Science, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Sapporo 060-0818.
  • | 3 3Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Sapporo 060-0818, Japan.

Abstract

OBJECTIVE

To investigate the activities of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) and serine proteases in the colorectal mucosa of Miniature Dachshunds (MDs) with inflammatory colorectal polyps (ICRPs).

ANIMALS

15 MDs with ICRPs and 5 dogs with non–ICRP-related large bowel diarrhea (controls).

PROCEDURES

Zymographic methods were used to evaluate the activities of MMP-2, MMP-9, latent forms of MMP-2 and MMP-9 (pro–MMP-2 and pro–MMP-9), and serine proteases in inflamed and noninflamed tissue samples from MDs with ICRPs and in noninflamed tissue samples from control dogs. The associations of serine protease activities with MMP-2 or MMP-9 activity were also analyzed.

RESULTS

Activities of pro–MMP-2 and pro–MMP-9 were detected in most tissue samples, regardless of the tissue type, whereas activities of MMP-2 and MMP-9 were not detected in control tissue samples. In the inflamed tissue samples from MDs with ICRPs, the activities of MMP-2, pro–MMP-9, and MMP-9 were significantly higher than those in the noninflamed tissue samples from those dogs. Serine protease activities were significantly higher in the inflamed and noninflamed tissue samples from MDs with ICRP, compared with findings for control tissue samples. A weak correlation was detected between serine protease activities and MMP-9 activity.

CONCLUSIONS AND CLINICAL RELEVANCE

Study results suggested that gelatinase and serine protease activities are upregulated in the colorectal mucosa of MDs with ICRPs, possibly contributing to the pathogenesis of this disease through the functions of these enzymes in degradation of extracellular matrix and promotion of inflammatory cell migration and inflammatory responses.

Abstract

OBJECTIVE

To investigate the activities of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) and serine proteases in the colorectal mucosa of Miniature Dachshunds (MDs) with inflammatory colorectal polyps (ICRPs).

ANIMALS

15 MDs with ICRPs and 5 dogs with non–ICRP-related large bowel diarrhea (controls).

PROCEDURES

Zymographic methods were used to evaluate the activities of MMP-2, MMP-9, latent forms of MMP-2 and MMP-9 (pro–MMP-2 and pro–MMP-9), and serine proteases in inflamed and noninflamed tissue samples from MDs with ICRPs and in noninflamed tissue samples from control dogs. The associations of serine protease activities with MMP-2 or MMP-9 activity were also analyzed.

RESULTS

Activities of pro–MMP-2 and pro–MMP-9 were detected in most tissue samples, regardless of the tissue type, whereas activities of MMP-2 and MMP-9 were not detected in control tissue samples. In the inflamed tissue samples from MDs with ICRPs, the activities of MMP-2, pro–MMP-9, and MMP-9 were significantly higher than those in the noninflamed tissue samples from those dogs. Serine protease activities were significantly higher in the inflamed and noninflamed tissue samples from MDs with ICRP, compared with findings for control tissue samples. A weak correlation was detected between serine protease activities and MMP-9 activity.

CONCLUSIONS AND CLINICAL RELEVANCE

Study results suggested that gelatinase and serine protease activities are upregulated in the colorectal mucosa of MDs with ICRPs, possibly contributing to the pathogenesis of this disease through the functions of these enzymes in degradation of extracellular matrix and promotion of inflammatory cell migration and inflammatory responses.

Contributor Notes

Address correspondence to Dr. Takiguchi (mtaki@vetmed.hokudai.ac.jp).