{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:15:03Z","timestamp":1788527703732,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8217030531"],"award-info":[{"award-number":["8217030531"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["8217030531"],"award-info":[{"award-number":["8217030531"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shanghai Science and Technology Action Plan","award":["23JC1401202"],"award-info":[{"award-number":["23JC1401202"]}]},{"name":"Joint Training Postdoctoral Program of Shanghai Jiao Tong University School of Medicine","award":["BH001"],"award-info":[{"award-number":["BH001"]}]},{"award":["BH001"],"award-info":[{"award-number":["BH001"]}],"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Although the prevalence of acute kidney injury and chronic kidney disease remains high and effective therapeutic targets remain scarce, significant progress has been made in recent years across the following major directions: G2\/M phase cell cycle arrest, DNA damage, mitochondrial dysfunction, hypoxia-inducible factor signaling, dysregulated autophagy, and epigenetic alterations. RGC-32 is abundantly expressed in all tubular segments of normal renal tissues and is primarily localized to the cytoplasm and perinuclear region of renal tubular epithelial cells. Moreover, RGC-32 is involved in cell cycle regulation as well as cell proliferation and differentiation. To explore the functional role of RGC-32 in renal repair after acute ischemia\u2013reperfusion injury, we utilized CRISPR-Cas9 technology combined with Cre\/loxP recombination to generate a novel, renal tubule-specific RGC-32 knockout mouse model and systematically characterized its phenotype. Our findings demonstrate that renal tubule-specific RGC-32 deficiency does not impair normal growth or baseline renal function but alters the distribution of peripheral blood T lymphocyte subsets; whether this alteration contributes to renal immune regulation remains to be determined by future functional studies. More importantly, upon IRI, RGC-32 knockout in renal tubules leads to significantly aggravated renal dysfunction, elevated injury markers, and a possible association with enhanced chronic fibrosis.<\/jats:p>","DOI":"10.3390\/biology15171535","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T12:20:46Z","timestamp":1788524446000},"page":"1535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tubule-Specific RGC-32 Knockout Exhibits Direct and Progressive Aggravating Activity Against Renal Function in an Ischemia\u2013Reperfusion Mouse Model"],"prefix":"10.3390","volume":"15","author":[{"given":"Yan","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Nephrology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2197-0781","authenticated-orcid":false,"given":"Wenyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/S0140-6736(18)31694-5","article-title":"Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: Reference and alternative scenarios for 2016-40 for 195 countries and territories","volume":"392","author":"Foreman","year":"2018","journal-title":"Lancet"},{"key":"ref_2","unstructured":"GBD Chronic Kidney Disease Collaboration (2020). 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