Transglutaminase 3 crosslinks the secreted gel-forming mucus component Mucin-2 and stabilizes the colonic mucus layer

• The colonic mucus layer is organized as a two-layered system providing a physical barrier against pathogens and simultaneously harboring the commensal flora. The factorscontributing to the organization of this gel network are not well understood. In this study, the impact of transglutaminase activity on this architecture was analyzed. Here, we show that transglutaminase TGM3 is the major transglutaminase-isoform expressed and synthesized in the colon. Furthermore, intrinsic extracellular transglutaminase activity in the secreted mucus was demonstrated in vitro and ex vivo. Absence of this acyl-transferase activity resulted in faster degradation of the major mucus component the MUC2 mucin and changed the biochemical properties of mucus. Finally, TGM3-deficient mice showed an early increased susceptibility to Dextran Sodium Sulfate-induced colitis. Here, we report that natural isopeptide cross-linking by TGM3 is important for mucus homeostasis and protection of the colon from inflammation, reducing the risk of colitis. © 2022, The Author(s).

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

biodegradation

enzyme

enzyme activity

gel

homeostasis

mucus

mucin 2

protein glutamine gamma glutamyltransferase

animal

colitis

colon

metabolism

mouse

Animals

Mice

Mucin-2

Transglutaminases

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)