Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/102362
PIRA download icon_1.1View/Download Full Text
DC FieldValueLanguage
dc.contributorDepartment of Applied Biology and Chemical Technology-
dc.contributorResearch Center for Chinese Medicine Innovation-
dc.creatorYu, Qen_US
dc.creatorLi, Cen_US
dc.creatorNiu, Qen_US
dc.creatorWang, Jen_US
dc.creatorChe, Zen_US
dc.creatorLei, Ken_US
dc.creatorRen, Hen_US
dc.creatorMa, Ben_US
dc.creatorRen, Yen_US
dc.creatorLuo, Pen_US
dc.creatorFan, Zen_US
dc.creatorZhang, Hen_US
dc.creatorLiu, Zen_US
dc.creatorTipoe, GLen_US
dc.creatorXiao, Jen_US
dc.date.accessioned2023-10-18T07:51:34Z-
dc.date.available2023-10-18T07:51:34Z-
dc.identifier.issn2211-3835en_US
dc.identifier.urihttp://hdl.handle.net/10397/102362-
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.rights© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rightsThe following publication Yu, Q., Li, C., Niu, Q., Wang, J., Che, Z., Lei, K., ... & Xiao, J. (2023). Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis. Acta Pharmaceutica Sinica B, 13(6), 2628-2644 is availale at https://doi.org/10.1016/j.apsb.2023.03.008.en_US
dc.subjectAutophagosome maturationen_US
dc.subjectAutophagyen_US
dc.subjectCyclooxygenase 1en_US
dc.subjectInflammationen_US
dc.subjectLipid metabolismen_US
dc.subjectNonalcoholic fatty liver diseaseen_US
dc.subjectPhosphatidylinositol 3-phosphateen_US
dc.subjectPhosphoinositide interacting 2en_US
dc.subjectWD repeat domainen_US
dc.titleHepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitisen_US
dc.typeJournal/Magazine Articleen_US
dc.identifier.spage2628en_US
dc.identifier.epage2644en_US
dc.identifier.volume13en_US
dc.identifier.issue6en_US
dc.identifier.doi10.1016/j.apsb.2023.03.008en_US
dcterms.abstractThe mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet–induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1–WIPI2 axis may be a novel therapeutic strategy for NASH.-
dcterms.accessRightsopen accessen_US
dcterms.bibliographicCitationActa pharmaceutica sinica B, June 2023, v. 13, no. 6, p. 2628-2644en_US
dcterms.isPartOfActa pharmaceutica sinica Ben_US
dcterms.issued2023-06-
dc.identifier.scopus2-s2.0-85152515798-
dc.identifier.eissn2211-3843en_US
dc.description.validate202310 bcvc-
dc.description.oaVersion of Recorden_US
dc.identifier.FolderNumberOA_Scopus/WOS-
dc.description.fundingSourceOthersen_US
dc.description.fundingTextNational Natural Science Foundation of China; University of Hong Kong; Natural Science Foundation of Shandong Provinceen_US
dc.description.pubStatusPublisheden_US
Appears in Collections:Journal/Magazine Article
Files in This Item:
File Description SizeFormat 
1-s2.0-S2211383523000977-main.pdf5.3 MBAdobe PDFView/Open
Open Access Information
Status open access
File Version Version of Record
Access
View full-text via PolyU eLinks SFX Query
Show simple item record

Page views

53
Citations as of Jun 16, 2024

Downloads

26
Citations as of Jun 16, 2024

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.