Clot-Stabilizing Enzyme Heals Colitis Damage in Mice and Shows Potential Wider Applications
The thrombin-activated transglutaminase factor XIII (FXIII) plays an important supportive role in the repair of colitis-induced mucosal damage in mice, according to research led by Joseph Palumbo, MD, a scientist in the Cancer and Blood Diseases Institute.
FXIII is best known as the enzyme that stabilizes fibrin clots. However, new findings published in PLOS ONE demonstrates that FXIII also plays a larger-than-expected role in tissue regeneration.
“Until our published report, the only direct evidence for a contribution of FXIII to tissue remodeling was for incisional skin wounds,” Palumbo says. “Our findings illustrate the potential possibilities of utilizing FXIII to resolve a wide range of tissue injuries.”
Palumbo, in collaboration with Novo Nordisk scientists Christina Andersson and Brian Lauritzen, evaluated how colitis-challenged mice responded when treated with recombinant human FXIII-A (rFXIII). They found that wildtype (WT) mice and mice genetically bred to lack the FXIII enzyme developed comparable mucosal damage when challenged with dextran sulfate sodium (DSS) to induce colitis symptoms. However, the FXIII-deficient mice failed to resolve the damage after DSS was withdrawn.
Treating mice with rFXIII significantly mitigated the clinical signs of colitis (e.g., weight loss, intestinal bleeding, diarrhea) while also largely resolving mucosal ulceration. Most strikingly, the benefit was not limited to FXIII-deficient animals. Control mice with normal FXIII gene expression also demonstrated a dramatic improvement in mucosal repair when treated with rFXIII following colitis challenge.
Further research is needed to determine the ultimate clinical utility of FXIII in IBD. However, the impact of this work may extend beyond IBD.
“For example, Matthew Flick in Experimental Hematology has published work detailing the contribution of FXIII to inflammatory arthritis pathogenesis, and Eric Mullins in Hematology has findings suggesting FXIII is linked to neuroinflammatory disease,” Palumbo says. “Furthermore, FXIII may play a fundamental role in cardiac tissue repair, another area of intense interest for our group.”
