Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes.
Animals
Bile Ducts
/ cytology
Cell Line
Cellular Senescence
/ genetics
Disease Models, Animal
Fatty Acid Elongases
/ genetics
Fatty Acids, Nonesterified
Hepatocytes
/ metabolism
Humans
Lipogenesis
/ genetics
Mice
Mice, Knockout
MicroRNAs
/ genetics
Non-alcoholic Fatty Liver Disease
/ genetics
Phenotype
Receptors, G-Protein-Coupled
/ genetics
Receptors, Gastrointestinal Hormone
/ genetics
Secretin
/ genetics
Up-Regulation
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
11
04
2021
received:
18
11
2020
accepted:
20
04
2021
pubmed:
1
5
2021
medline:
11
1
2022
entrez:
30
4
2021
Statut:
ppublish
Résumé
Human NAFLD is characterized at early stages by hepatic steatosis, which may progress to NASH when the liver displays microvesicular steatosis, lobular inflammation, and pericellular fibrosis. The secretin (SCT)/secretin receptor (SCTR) axis promotes biliary senescence and liver fibrosis in cholestatic models through down-regulation of miR-125b signaling. We aim to evaluate the effect of disrupting biliary SCT/SCTR/miR-125b signaling on hepatic steatosis, biliary senescence, and liver fibrosis in NAFLD/NASH. In vivo, 4-week-old male wild-type, Sct The biliary SCT/SCTR/miR-125b axis promotes liver steatosis by up-regulating lipid biosynthesis gene Elovl1. Targeting the biliary SCT/SCTR/miR-125b axis may be key for ameliorating phenotypes of human NAFLD/NASH.
Sections du résumé
BACKGROUND AND AIMS
Human NAFLD is characterized at early stages by hepatic steatosis, which may progress to NASH when the liver displays microvesicular steatosis, lobular inflammation, and pericellular fibrosis. The secretin (SCT)/secretin receptor (SCTR) axis promotes biliary senescence and liver fibrosis in cholestatic models through down-regulation of miR-125b signaling. We aim to evaluate the effect of disrupting biliary SCT/SCTR/miR-125b signaling on hepatic steatosis, biliary senescence, and liver fibrosis in NAFLD/NASH.
APPROACH AND RESULTS
In vivo, 4-week-old male wild-type, Sct
CONCLUSION
The biliary SCT/SCTR/miR-125b axis promotes liver steatosis by up-regulating lipid biosynthesis gene Elovl1. Targeting the biliary SCT/SCTR/miR-125b axis may be key for ameliorating phenotypes of human NAFLD/NASH.
Identifiants
pubmed: 33928675
doi: 10.1002/hep.31871
pmc: PMC8782246
mid: NIHMS1700557
doi:
Substances chimiques
ELOVL1 protein, human
0
Elovl1 protein, mouse
0
Fatty Acids, Nonesterified
0
MIRN125 microRNA, human
0
MicroRNAs
0
Mirn125 microRNA, mouse
0
Receptors, G-Protein-Coupled
0
Receptors, Gastrointestinal Hormone
0
secretin receptor
0
Secretin
1393-25-5
Fatty Acid Elongases
EC 2.3.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1845-1863Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK108959
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121330
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110035
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107310
Pays : United States
Organisme : BLRD VA
ID : I01 BX000574
Pays : United States
Organisme : BLRD VA
ID : I01 BX003031
Pays : United States
Organisme : BLRD VA
ID : IK6 BX004601
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119421
Pays : United States
Organisme : BLRD VA
ID : IK6 BX005226
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA025997
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122796
Pays : United States
Organisme : BLRD VA
ID : I01 BX001724
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK076898
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115184
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA028711
Pays : United States
Informations de copyright
© 2021 by the American Association for the Study of Liver Diseases.
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