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Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression
Ist Teil von
International journal of molecular sciences, 2024-02, Vol.25 (4), p.2401
Ort / Verlag
Switzerland: MDPI AG
Erscheinungsjahr
2024
Quelle
MEDLINE
Beschreibungen/Notizen
We recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn
homeostasis in the heart. Zn
has also been implicated in the regulation of intestinal redox and microbial homeostasis. This study aims to investigate the role of TRPC6-mediated Zn
influx in the stress resistance of the intestine. The expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using the GEO database. Systemic TRPC3 knockout (KO) and TRPC6 KO mice were treated with dextran sulfate sodium (DSS) to induce colitis. The Zn
concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6 KO mice, but not TRPC3 KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in the TRPC6 KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn
concentration. We suggest that TRPC6-mediated Zn
influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.