{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:20:56Z","timestamp":1780568456167,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00208093"],"award-info":[{"award-number":["RS-2023-00208093"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00350482"],"award-info":[{"award-number":["RS-2024-00350482"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic kidney disease (CKD) involves ongoing impairment of kidney function and structural changes. Previous studies indicated that males have a substantially higher prevalence of CKD than those observed in females. Here, we compared the gender differences in CKD development by comparing age-matched male and female mice subjected to a 0.25% adenine diet (AD) for two weeks. Male mice showed a significantly greater decrease in kidney function than female mice, as evidenced by the elevated blood urea nitrogen levels (M-AD: 160 \u00b1 5 mg\/dL, F-AD: 90 \u00b1 4 mg\/dL; p &lt; 0.001). Furthermore, male mice kidneys exhibited pronounced tubule dilation and kidney damage, as detected by histological and biochemical methods. The extent of fibrosis was quantified using multiple biological methods, revealing a greater degree of fibrosis in male kidneys. We next indicated the inflammatory responses in the kidneys. Similar to the extent of fibrosis, AD-fed male mice showed significantly increased levels of pro-inflammatory markers, including cytokine expression and infiltration of immune cell, compared to female mice. Based on in vivo observations, the anti-inflammatory and anti-fibrotic effects of 17\u03b2-estradiol (E2) were further evaluated in vitro conditions. E2 pre-treatment significantly reduced lipopolysaccharide-induced inflammatory response through inhibition of the nuclear factor-kappa B (NF-\u03baB) pathway in NRK52E renal epithelial cells. In NRK49F renal fibroblasts, E2 pre-treatment also reduced TGF\u03b2-induced fibrotic responses. We further demonstrated that E2 markedly decreased fibrosis and inflammation in AD-fed mouse kidneys. Our observations revealed that male mice kidneys exhibited a heightened inflammatory and fibrotic response compared to female mice kidneys. Additionally, our findings suggest that the observed sex differences may be partially attributed to the potential anti-inflammatory and anti-fibrotic effects of E2.<\/jats:p>","DOI":"10.3390\/ijms26031358","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T04:47:31Z","timestamp":1738817251000},"page":"1358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Gender Differences in Adenine Diet-Induced Kidney Toxicity: The Impact of 17\u03b2-Estradiol on Renal Inflammation and Fibrosis"],"prefix":"10.3390","volume":"26","author":[{"given":"Sugyeong","family":"Ha","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjung","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong Moo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-2494","authenticated-orcid":false,"given":"Donghwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Functional Food Materials Research Group, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3215-8828","authenticated-orcid":false,"given":"Hae Young","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Wung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of chronic kidney disease: An update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int. 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