PMID- 38081680
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20231216
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 154
IP  - 1
DP  - 2024 Jan
TI  - Transient receptor potential melastatin 2 is involved in trinitrobenzene sulfonic 
      acid-induced acute and chronic colitis-associated fibrosis progression in mice.
PG  - 18-29
LID - S1347-8613(23)00068-3 [pii]
LID - 10.1016/j.jphs.2023.11.004 [doi]
AB  - Crohn's disease, a chronic and recurrent gastrointestinal disease, frequently 
      causes intestinal fibrosis. Transient receptor potential melastatin 2 (TRPM2), a 
      non-selective cation channel, is activated by reactive oxygen species. This study 
      investigated the role of TRPM2 in acute colitis and chronic colitis-associated 
      fibrosis progression. Acute colitis and chronic colitis-associated fibrosis were 
      induced in TRPM2-deficient (TRPM2KO) and wild-type (WT) mice through single and 
      repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). 
      Bone marrow-derived macrophages (BMDMs) from WT and TRPM2KO mice were stimulated 
      using H(2)O(2). In WT mice, a single TNBS injection induced acute colitis with 
      upregulated inflammatory cytokines/chemokines and Th1/Th17-related cytokines, 
      while repeated TNBS injections induced chronic colitis-associated fibrosis with 
      upregulation of fibrogenic factors and Th2-related cytokines. Acute colitis and 
      chronic colitis-associated fibrosis with cytokines/chemokine upregulation and 
      fibrogenic factors were considerably suppressed in TRPM2KO mice. Treating BMDMs 
      with H(2)O(2) increased cytokine/chemokine expression and JNK, ERK, and p38 
      phosphorylation; however, these responses were significantly less in TRPM2KO than 
      in WT mice. These findings suggest that TRPM2 contributes to acute colitis 
      progression via Th1/Th17-mediated immune responses. Furthermore, TRPM2 may be 
      directly involved in colitis-associated fibrosis induction, likely due to the 
      regulation of Th2/TGF-beta1-mediated fibrogenesis in addition to a consequence of 
      acute colitis progression.
CI  - Copyright (c) 2023 The Authors. Production and hosting by Elsevier B.V. All rights 
      reserved.
FAU - Nakamoto, Tomohiro
AU  - Nakamoto T
AD  - Division of Pathological Science, Laboratory of Pharmacology and Experimental 
      Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan.
FAU - Matsumoto, Kenjiro
AU  - Matsumoto K
AD  - Division of Pathological Science, Laboratory of Pharmacology and Experimental 
      Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan.
FAU - Yasuda, Hiroyuki
AU  - Yasuda H
AD  - Division of Pathological Science, Laboratory of Pharmacology and Experimental 
      Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan.
FAU - Mori, Yasuo
AU  - Mori Y
AD  - Department of Synthetic Chemistry and Biological Chemistry, Graduate of 
      Engineering, Kyoto University, Kyoto, Japan.
FAU - Kato, Shinichi
AU  - Kato S
AD  - Division of Pathological Science, Laboratory of Pharmacology and Experimental 
      Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan. Electronic address: 
      skato@mb.kyoto-phu.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20231130
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (TRPM Cation Channels)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid)
RN  - 0 (Cytokines)
RN  - 0 (Trinitrobenzenes)
RN  - 0 (Chemokines)
RN  - 0 (TRPM2 protein, mouse)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Colon/metabolism
MH  - *TRPM Cation Channels/genetics
MH  - Hydrogen Peroxide/metabolism
MH  - Trinitrobenzenesulfonic Acid/adverse effects/metabolism
MH  - *Colitis/chemically induced/complications/genetics
MH  - Cytokines/metabolism
MH  - Trinitrobenzenes/metabolism
MH  - Chemokines/adverse effects/metabolism
MH  - Fibrosis
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - Colitis
OT  - Cytokines/chemokines
OT  - Fibrosis
OT  - Macrophages
OT  - Transient receptor potential melastatin 2 (TRPM2)
COIS- Declaration of competing interest The authors declare no conflicts of interest.
EDAT- 2023/12/12 00:42
MHDA- 2023/12/17 13:19
CRDT- 2023/12/11 20:55
PHST- 2023/08/30 00:00 [received]
PHST- 2023/11/02 00:00 [revised]
PHST- 2023/11/27 00:00 [accepted]
PHST- 2023/12/17 13:19 [medline]
PHST- 2023/12/12 00:42 [pubmed]
PHST- 2023/12/11 20:55 [entrez]
AID - S1347-8613(23)00068-3 [pii]
AID - 10.1016/j.jphs.2023.11.004 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2024 Jan;154(1):18-29. doi: 10.1016/j.jphs.2023.11.004. Epub 
      2023 Nov 30.