Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression.
Kazuhiro NishiyamaYuri KatoAkiyuki NishimuraXinya MiRyu NagataYasuo MoriYasu-Taka AzumaMotohiro NishidaPublished in: International journal of molecular sciences (2024)
We recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn 2+ homeostasis in the heart. Zn 2+ has also been implicated in the regulation of intestinal redox and microbial homeostasis. This study aims to investigate the role of TRPC6-mediated Zn 2+ 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 2+ 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 2+ concentration. We suggest that TRPC6-mediated Zn 2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.
Keyphrases
- vascular smooth muscle cells
- newly diagnosed
- heavy metals
- disease activity
- end stage renal disease
- weight loss
- systemic lupus erythematosus
- ejection fraction
- angiotensin ii
- ulcerative colitis
- gene expression
- high fat diet induced
- emergency department
- body mass index
- oxidative stress
- stress induced
- risk assessment
- patient reported outcomes
- nuclear factor
- wild type
- subarachnoid hemorrhage
- rheumatoid arthritis patients
- glycemic control
- smoking cessation