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Forkhead box protein M1 (FoxM1), a transcription factor of the Forkhead box (Fox) protein super family, has been reported to promote tumor formation, inflammation and fibrosis in many organs. However, the role and mechanism of FoxM1 in regulation of ADPKD progression is still poorly understood. Here, we show that FoxM1 is an important regulator of cyst growth in ADPKD. FoxM1 is upregulated in cyst-lining epithelial cells in Pkd1 mutant mouse kidneys and human ADPKD kidneys. FoxM1 promotes cystic renal epithelial cell proliferation by increasing the expression of Akt and Stat3 and the activation of ERK and Rb. FoxM1 also regulates cystic renal epithelial cell apoptosis through NF-\u03baB signaling pathways. In addition, FoxM1 regulates the recruitment and retention of macrophages in Pkd1 mutant mouse kidneys, a process that is associated with FoxM1-mediated upregulation of monocyte chemotactic protein 1. Targeting FoxM1 with its specific inhibitor, FDI-6, delays cyst growth in rapidly progressing and slowly progressing Pkd1 mutant mouse kidneys. This study suggests that FoxM1 is a central and upstream regulator of ADPKD pathogenesis and provides a rationale for targeting FoxM1 as a therapeutic strategy for ADPKD treatment.<\/jats:p>","DOI":"10.1093\/hmg\/ddac273","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:53:37Z","timestamp":1667408017000},"page":"1114-1126","source":"Crossref","is-referenced-by-count":8,"title":["Transcription factor FoxM1 promotes cyst growth in PKD1 mutant ADPKD"],"prefix":"10.1093","volume":"32","author":[{"given":"Wenyan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Research Center for Differentiation and Development of TCM Basic Theory , Jiangxi Province Key Laboratory of TCM Etiopathogenesis, , Nanchang, Jiangxi 330004 , China"},{"name":"Jiangxi University of Chinese Medicine , Jiangxi Province Key Laboratory of TCM Etiopathogenesis, , Nanchang, Jiangxi 330004 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guojuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Department of Oncology , , Nanchang 330006 , China"},{"name":"The Affiliated Hospital of University of Jiangxi of Traditional Chinese Medicine , , Nanchang 330006 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda Xiaoyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Eye Institute of Shaanxi Province; Xi\u2019an First Hospital , Xi\u2019an 710002, Shaanxi Province , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuehong","family":"Gui","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie Xia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P","family":"Calvet","sequence":"additional","affiliation":[{"name":"Research Center for Differentiation and Development of TCM Basic Theory , Jiangxi Province Key Laboratory of TCM Etiopathogenesis, , Nanchang, Jiangxi 330004 , China"},{"name":"Jiangxi University of Chinese Medicine , Jiangxi Province Key Laboratory of TCM Etiopathogenesis, , Nanchang, Jiangxi 330004 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8135-342X","authenticated-orcid":false,"given":"Xiaogang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"},{"name":"Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 , USA"},{"name":"Mayo Clinic , , Rochester, MN 55905 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"2023032011072868600_","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/nrneph.2011.196","article-title":"Polycystic kidney disease in 2011: connecting the dots toward a polycystic kidney disease therapy","volume":"8","author":"Torres","year":"2011","journal-title":"Nat. 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