1. What role does the MMP9-PLG axis play in IBD?
The MMP9-PLG axis plays a significant role in inflammatory bowel diseases (IBD). Over 200 loci have been associated with human IBD, but identifying causative factors is challenging. Zoobiquity, an approach that examines cross-species risk factors, has been used to study inflammatory colorectal polyps (ICRPs) in Miniature Dachshunds (MDs). Through whole-exome sequencing, Yamasaki et al. identified SNPs in PLG associated with pathology in MDs. Increased degradation of plasminogen was observed in colonic lesions of ICRP-affected MDs with risk SNPs. IL-6 amplifier-mediated MMP9 expression cleaves plasminogen containing the risk alleles in colonic lesions of MDs and intestinal lesions of patients with ulcerous colitis or Crohn's disease. These findings suggest a role for the MMP9-plasminogen axis in human IBDs, highlighting the potential for using zoobiquity to identify therapeutic targets for human diseases.
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