Promotion of wound healing by acetate in murine colonic epithelial cell via c-Jun N-terminal kinase activation.
Acetates
/ administration & dosage
Animals
Cells, Cultured
Colitis
/ drug therapy
Colon
/ cytology
Disease Models, Animal
Epithelial Cells
/ pathology
Fatty Acids, Volatile
/ pharmacology
JNK Mitogen-Activated Protein Kinases
/ metabolism
MAP Kinase Signaling System
/ drug effects
Male
Mice, Inbred C57BL
Wound Healing
/ drug effects
rho-Associated Kinases
/ metabolism
Acetate
Colonic epithelial cell
Inflammatory bowel disease
Wound healing
Journal
Journal of gastroenterology and hepatology
ISSN: 1440-1746
Titre abrégé: J Gastroenterol Hepatol
Pays: Australia
ID NLM: 8607909
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
12
02
2019
revised:
20
12
2019
accepted:
16
01
2020
pubmed:
22
1
2020
medline:
11
11
2020
entrez:
22
1
2020
Statut:
ppublish
Résumé
Mucosal healing is an important clinical goal in patients with inflammatory bowel disease. Recently, short-chain fatty acids (SCFAs) have been reported to have multifaceted effects to host. However, the effects of SCFAs on wound healing in intestinal epithelial cells are unclear. In the present study, we investigated the effects of acetate, one of the major SCFAs, on the wound healing of murine colonic epithelial cells. Young adult mouse colonic epithelial cells were used to determine the effect of acetate using wound healing assay. Mitogen-activated protein kinase and Rho kinase inhibitor were used to elucidate intracellular signal of wound healing treated with acetate. Meanwhile, Rho activation assays were utilized to measure Rho activation levels. To assess in vivo effects, C57B6 mice with dextran sodium sulfate for 7 days were treated with enema administration of acetate for 7 days. Body weight, disease activity index, colon length, and mucosal break ratio in histology were examined. Acetate enhanced wound healing and fluorescence intensity of actin stress fiber compared with control. These effects were canceled with pretreatment of c-Jun N-terminal kinase (JNK) inhibitor or Rho kinase inhibitor. Furthermore, JNK inhibitor reduced the activation of Rho induced by acetate. In the dextran sodium sulfate-induced colitis model, the mice with enema treatment of acetate significantly exhibited recovery. In this study, we demonstrated that acetate promoted murine colonic epithelial cell wound healing via activation of JNK and Rho signaling pathways. These findings suggested that acetate could have applications as a therapeutic agent for patients with intestinal mucosal damage, such as inflammatory bowel disease.
Sections du résumé
BACKGROUND AND AIM
OBJECTIVE
Mucosal healing is an important clinical goal in patients with inflammatory bowel disease. Recently, short-chain fatty acids (SCFAs) have been reported to have multifaceted effects to host. However, the effects of SCFAs on wound healing in intestinal epithelial cells are unclear. In the present study, we investigated the effects of acetate, one of the major SCFAs, on the wound healing of murine colonic epithelial cells.
METHODS
METHODS
Young adult mouse colonic epithelial cells were used to determine the effect of acetate using wound healing assay. Mitogen-activated protein kinase and Rho kinase inhibitor were used to elucidate intracellular signal of wound healing treated with acetate. Meanwhile, Rho activation assays were utilized to measure Rho activation levels. To assess in vivo effects, C57B6 mice with dextran sodium sulfate for 7 days were treated with enema administration of acetate for 7 days. Body weight, disease activity index, colon length, and mucosal break ratio in histology were examined.
RESULTS
RESULTS
Acetate enhanced wound healing and fluorescence intensity of actin stress fiber compared with control. These effects were canceled with pretreatment of c-Jun N-terminal kinase (JNK) inhibitor or Rho kinase inhibitor. Furthermore, JNK inhibitor reduced the activation of Rho induced by acetate. In the dextran sodium sulfate-induced colitis model, the mice with enema treatment of acetate significantly exhibited recovery.
CONCLUSIONS
CONCLUSIONS
In this study, we demonstrated that acetate promoted murine colonic epithelial cell wound healing via activation of JNK and Rho signaling pathways. These findings suggested that acetate could have applications as a therapeutic agent for patients with intestinal mucosal damage, such as inflammatory bowel disease.
Substances chimiques
Acetates
0
Fatty Acids, Volatile
0
rho-Associated Kinases
EC 2.7.11.1
JNK Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1171-1179Subventions
Organisme : Ministry of Agriculture, Forestry and Fisheries
ID : 16824414
Organisme : Japan Society for the Promotion of Science
ID : 15K08313
Organisme : Japan Society for the Promotion of Science
ID : 16K09322
Organisme : Japan Society for the Promotion of Science
ID : 16675576
Informations de copyright
© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
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