Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/102362
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Applied Biology and Chemical Technology | - |
dc.contributor | Research Center for Chinese Medicine Innovation | - |
dc.creator | Yu, Q | en_US |
dc.creator | Li, C | en_US |
dc.creator | Niu, Q | en_US |
dc.creator | Wang, J | en_US |
dc.creator | Che, Z | en_US |
dc.creator | Lei, K | en_US |
dc.creator | Ren, H | en_US |
dc.creator | Ma, B | en_US |
dc.creator | Ren, Y | en_US |
dc.creator | Luo, P | en_US |
dc.creator | Fan, Z | en_US |
dc.creator | Zhang, H | en_US |
dc.creator | Liu, Z | en_US |
dc.creator | Tipoe, GL | en_US |
dc.creator | Xiao, J | en_US |
dc.date.accessioned | 2023-10-18T07:51:34Z | - |
dc.date.available | 2023-10-18T07:51:34Z | - |
dc.identifier.issn | 2211-3835 | en_US |
dc.identifier.uri | http://hdl.handle.net/10397/102362 | - |
dc.language.iso | en | en_US |
dc.publisher | Elsevier 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.rights | The 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.subject | Autophagosome maturation | en_US |
dc.subject | Autophagy | en_US |
dc.subject | Cyclooxygenase 1 | en_US |
dc.subject | Inflammation | en_US |
dc.subject | Lipid metabolism | en_US |
dc.subject | Nonalcoholic fatty liver disease | en_US |
dc.subject | Phosphatidylinositol 3-phosphate | en_US |
dc.subject | Phosphoinositide interacting 2 | en_US |
dc.subject | WD repeat domain | en_US |
dc.title | Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.spage | 2628 | en_US |
dc.identifier.epage | 2644 | en_US |
dc.identifier.volume | 13 | en_US |
dc.identifier.issue | 6 | en_US |
dc.identifier.doi | 10.1016/j.apsb.2023.03.008 | en_US |
dcterms.abstract | The 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.accessRights | open access | en_US |
dcterms.bibliographicCitation | Acta pharmaceutica sinica B, June 2023, v. 13, no. 6, p. 2628-2644 | en_US |
dcterms.isPartOf | Acta pharmaceutica sinica B | en_US |
dcterms.issued | 2023-06 | - |
dc.identifier.scopus | 2-s2.0-85152515798 | - |
dc.identifier.eissn | 2211-3843 | en_US |
dc.description.validate | 202310 bcvc | - |
dc.description.oa | Version of Record | en_US |
dc.identifier.FolderNumber | OA_Scopus/WOS | - |
dc.description.fundingSource | Others | en_US |
dc.description.fundingText | National Natural Science Foundation of China; University of Hong Kong; Natural Science Foundation of Shandong Province | en_US |
dc.description.pubStatus | Published | en_US |
Appears in Collections: | Journal/Magazine Article |
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File | Description | Size | Format | |
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1-s2.0-S2211383523000977-main.pdf | 5.3 MB | Adobe PDF | View/Open |
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