{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:08:00Z","timestamp":1792757280769,"version":"4.5.0"},"reference-count":21,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science and Technology (MEXT)","award":["JP24K20259"],"award-info":[{"award-number":["JP24K20259"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Class III alcohol dehydrogenase (ADH3), primarily localized in the liver and kidney, contributes to alcohol metabolism during chronic alcohol consumption (CAC). However, its role in kidney function remains unclear. This study investigated renal morphological changes associated with ADH3-mediated alcohol metabolism. Nine-week-old male wild-type (WT) and ADH3-deficient (Adh3-\/-) mice were administered 10% ethanol for 1 month. Histological analyses were performed using periodic acid\u2013Schiff (PAS) staining and electron microscopy. Serum biochemical parameters were also assessed. In WT mice, CAC induced an increase in cuboidal parietal epithelial cells (PECs) in Bowman\u2019s capsule, along with elevated testosterone levels in both serum and urine. Adh3-\/- mice showed increased PECs even in the control group, with similarly elevated serum testosterone in both control and ethanol-treated groups. These findings suggest that ADH3 is involved in testosterone metabolism, and that that metabolism is suppressed by CAC because ADH3 shifts toward ethanol metabolism. The resulting testosterone elevation may contribute to PEC proliferation. An increase in PECs observed even in Adh3-\/- control mice may also be caused by the lack of testosterone metabolism via ADH3. Thus, renal ADH3 may protect kidney structure through testosterone metabolism, but its role may be disturbed by CAC. This study highlights the role of ADH3 in the relationship between physiological steroid metabolism and alcoholic pathological abnormality in the kidney.<\/jats:p>","DOI":"10.3390\/ijms26136279","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Class III Alcohol Dehydrogenase Modulates Renal Parietal Epithelial Cell Transformation During Chronic Alcohol Consumption in Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Midori","family":"Katsuyama","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Okuda","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"},{"name":"Department of Plastic, Reconstructive & Aesthetic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamichi","family":"Ishizaki","sequence":"additional","affiliation":[{"name":"Department of Analytic Human Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Wada","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, Department of Internal Medicine, Nippon Kokan Fukuyama Hospital, 1844 Tsunoshita, Daimon-cho, Fukuyama, Hiroshima 721-0927, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyo","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Science, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Akimoto","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Science, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youkichi","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahito","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1060-927X","authenticated-orcid":false,"given":"Takeshi","family":"Haseba","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"},{"name":"Department of Legal Medicine, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0378-4274(84)90142-5","article-title":"Sex and strain differences in mouse kidney: Bowman\u2019s capsule morphology and susceptibility to chloroform","volume":"20","author":"Ahmadizadeh","year":"1984","journal-title":"Toxicol. Lett."},{"key":"ref_2","first-page":"485","article-title":"Sex difference and fine structure on epithelium cells of Bowman\u2019s capsule in mice (author\u2019s transl)","volume":"28","author":"Hamada","year":"1979","journal-title":"Jikken Dobutsu"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1292\/jvms.68.439","article-title":"Rodent renal structure differs among species","volume":"68","author":"Ichii","year":"2006","journal-title":"J. Vet. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1083\/jcb.35.2.435","article-title":"The columnar cells occurring in the parietal layer of Bowman\u2019s capsule. Cellular fine structure and protein transport","volume":"35","author":"Dietert","year":"1967","journal-title":"J. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.kint.2019.01.037","article-title":"Novel parietal epithelial cell subpopulations contribute to focal segmental glomerulosclerosis and glomerular tip lesions","volume":"96","author":"Kuppe","year":"2019","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1073\/pnas.83.9.2836","article-title":"Testosterone allosterically regulates ethanol oxidation by homo- and heterodimeric gamma-subunit-containing isozymes of human alcohol dehydrogenase","volume":"83","author":"Falchuk","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"408190","DOI":"10.1155\/2012\/408190","article-title":"Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I) to ADH 3 (Class III) in Mouse","volume":"2012","author":"Haseba","year":"2012","journal-title":"Int. J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1111\/jgh.14260","article-title":"Metabolic pharmacokinetics of early chronic alcohol consumption mediated by liver alcohol dehydrogenases 1 and 3 in mice","volume":"33","author":"Okuda","year":"2018","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/alcalc\/agz091","article-title":"Roles of two major Alcohol Dehydrogenases, ADH1 (Class I) and ADH3 (Class III), in the adaptive enhancement of alcohol metabolism induced by chronic alcohol consumption in mice","volume":"55","author":"Haseba","year":"2020","journal-title":"Alc. Alc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1111\/j.1530-0277.1997.tb04480.x","article-title":"Regional restriction of alcohol\/retinol dehydrogenases along the mouse gastrointestinal epithelium","volume":"21","author":"Haselbeck","year":"1997","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.prostaglandins.2014.10.006","article-title":"Ethanol at low concentrations protects glomerular podocytes through alcohol dehydrogenase and 20-HETE","volume":"116\u2013117","author":"McCarthy","year":"2015","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_12","first-page":"340","article-title":"Role of class III alcohol dehydrogenase (ADH3) in renal pathological changes induced by chronic alcohol consumption in mice","volume":"9","author":"Katsuyama","year":"2021","journal-title":"J. Alcohol. Drug Depend."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1210\/endo-100-2-473","article-title":"Differential effect of hypophysectomy on the synthesis of beta-glucuronidase and other androgen-inducible enzymes in mouse kidney","volume":"100","author":"Swank","year":"1977","journal-title":"Endocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/jbt.20101","article-title":"Ethanol-induced alterations of the antioxidant defense system in rat kidney","volume":"19","author":"Dinu","year":"2005","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/hep.1840020312","article-title":"Effect of dihydrogenase on rat liver alcohol dehydrogenase activity","volume":"2","author":"Mezey","year":"1982","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF00491493","article-title":"Cytochemical correlates of structural sexual dimorphism in glandular tissues of the mouse. I. Studies of the renal glomerular capsule","volume":"44","author":"Hanker","year":"1975","journal-title":"Histochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/sj.ki.5002512","article-title":"Glomerulotubular disconnection in neonatal mice after relief of partial ureteral obstruction","volume":"72","author":"Thornhill","year":"2007","journal-title":"Kidney Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.redox.2015.06.021","article-title":"Chronic ethanol consumption induces mitochondrial protein acetylation and oxidative stress in the kidney","volume":"6","author":"Harris","year":"2015","journal-title":"Redox Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.freeradbiomed.2014.01.001","article-title":"Chronic ethanol ingestion induces oxidative kidney injury through taurine-inhibitable inflammation","volume":"69","author":"Latchoumycandane","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0006-2952(99)00065-9","article-title":"Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family","volume":"58","author":"Duester","year":"1999","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3177\/jnsv.41.527","article-title":"Changes in hepatic enzyme activities related to ethanol metabolism in mice following chronic ethanol administration","volume":"41","author":"Kishimoto","year":"1995","journal-title":"J. Nutr. Sci. Vitaminol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6279\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:01:11Z","timestamp":1760032871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,29]]},"references-count":21,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26136279"],"URL":"https:\/\/doi.org\/10.3390\/ijms26136279","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,29]]}}}