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Although reduced expression of FoxA2 has been associated with chronic liver diseases, hepatic progenitor cells (HPCs) that are activated in these circumstances express FoxA2. However, the functional effects and underlying mechanism of FoxA2 in HPCs are still unknown. As revealed by immunostaining, HPCs expressed FoxA2 in human cirrhotic livers and in the livers of choline\u2010deficient diet supplemented with ethionine (CDE) rats. Knocking down FoxA2 in HPCs isolated from CDE rats significantly increased cell proliferation and aerobic glycolysis. Moreover, gene transcription, protein expression, and the enzyme activities of hexokinase 2 (HK2) were upregulated, and blocking HK2 activities via 2\u2010deoxyglucose markedly reduced cell proliferation and aerobic glycolysis. Kyoto Encyclopedia of Genes and Genomes analysis revealed that FoxA2 knockdown enhanced the transcription of genes involved in the phosphatidylinositol 3\u2010kinase (PI3K)\/protein kinase B (Akt) pathway and triggered downstream Akt phosphorylation. Blocking the PI3K\/Akt pathway by Ly294002 inhibited HK2 activities, aerobic glycolysis, and cell proliferation in FoxA2\u2010knockdown cells. Therefore, FoxA2 plays an important role in the proliferation and inhibition of HPCs by suppressing PI3K\/Akt\/HK2\u2010regulated aerobic glycolysis.<\/jats:p>","DOI":"10.1002\/jcp.29759","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T08:30:34Z","timestamp":1591259434000},"page":"9524-9537","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["FoxA2 inhibits the proliferation of hepatic progenitor cells by reducing PI3K\/Akt\/HK2\u2010mediated glycolysis"],"prefix":"10.1002","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1395-2014","authenticated-orcid":false,"given":"Ping","family":"Wang","sequence":"first","affiliation":[{"name":"Liver Research Center, Beijing Friendship Hospital Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis National Clinical Research Center for Digestive Diseases Beijing 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