Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression.

Kazuhiro Nishiyama
,
Yuri Kato
ORCID logo ,
Akiyuki Nishimura
ORCID logo ,
Xinya Mi
,
Ryu Nagata
,
Yasuo Mori
,
Yasu-Taka Azuma
ORCID logo ,
Motohiro Nishida
*
Version 1 : Received: 1 February 2024 / Approved: 2 February 2024 / Online: 2 February 2024 (06:39:42 CET)

A peer-reviewed article of this Preprint also exists.

Nishiyama, K.; Kato, Y.; Nishimura, A.; Mi, X.; Nagata, R.; Mori, Y.; Azuma, Y.-T.; Nishida, M. Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression. Int. J. Mol. Sci. 2024, 25, 2401. Nishiyama, K.; Kato, Y.; Nishimura, A.; Mi, X.; Nagata, R.; Mori, Y.; Azuma, Y.-T.; Nishida, M. Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression. Int. J. Mol. Sci. 2024, 25, 2401.

Abstract

Zn2+ has been implicated in the regulation of intestinal redox and microbial homeostasis, and we recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in mammalian cells. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in stress resistance of intestine. Expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using GEO database. Systemic TRPC3-knockout (KO) and TRPC6-KO mice were treated with dextran sulphate sodium (DSS) to induce colitis. The Zn2+ 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 TRPC6-KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.

Keywords

Canonical transient receptor potential 6; Colitis; Stress resistance; Gut microbiota

Subject

Medicine and Pharmacology, Gastroenterology and Hepatology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.