Sphincter of Oddi Dysfunction Induces Gallstone by Inhibiting the Expression of ABCB11 via PKC-α.
ABCB11
Gallstones
PKC-α
Sphincter of Oddi
Sphincter of Oddi dysfunction (SOD)
Journal
Applied biochemistry and biotechnology
ISSN: 1559-0291
Titre abrégé: Appl Biochem Biotechnol
Pays: United States
ID NLM: 8208561
Informations de publication
Date de publication:
30 Dec 2023
30 Dec 2023
Historique:
accepted:
19
12
2023
medline:
2
1
2024
pubmed:
2
1
2024
entrez:
29
12
2023
Statut:
aheadofprint
Résumé
The abnormal increase of Oddi sphincter pressure and total bile duct pressure may play an important role in the formation of cholesterol stones, but the specific molecular mechanism is still unclear. This study aims to investigate it through in vitro and in vivo experiments. A mouse model of Oddi sphincter dysfunction was constructed by stone-inducing diet. We compared the two groups with PKC-α inhibitor GÖ6976 and PKC-α agonist thymeleatoxin. Oddi sphincter pressure and total bile duct pressure were measured. Biochemical analysis of total cholesterol, bile acid and bilirubin was then conducted. The histopathologic changes of bile duct were observed by HE staining and the ultrastructure of liver cells and surrounding tissues was observed by transmission electron microscopy. Through the above experiments, we found that the change of PKC-α expression may affect the formation process of gallstones. The relationship between PKC-α and ABCB11 was further verified by in vitro and in vivo experiments. Our results suggest that ABCB11 and PKC-α are co-expressed in the tubule membrane of hepatocytes and interact with each other in hepatocytes. The high cholesterol diet further enhances the activation of PKC-α and thus reduces the expression of ABCB11. The formation of cholesterol stones is associated with the down-regulation of ABCB11 expression in the tubule membrane of hepatocytes due to kinase signaling. This is the first study to demonstrate that sphincter of Oddi dysfunction induces gallstones through PKC-α inhibition of ABCB11 expression.
Identifiants
pubmed: 38158489
doi: 10.1007/s12010-023-04818-x
pii: 10.1007/s12010-023-04818-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : No.81870205
Organisme : National Natural Science Foundation of China
ID : No. 82000579
Organisme : Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province
ID : CXPJJH12000001-2020304
Organisme : Foundation research project of Qinghai province
ID : 2021-ZJ-719
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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