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However, the role of vitamin C as an epigenetic regulator in renal homeostasis and pathogenesis remains largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We showed that vitamin C deficiency leads to acute tubular necrosis (ATN) using a vitamin C\u2013deficient mouse model (\n                      <jats:italic toggle=\"yes\">Gulo<\/jats:italic>\n                      knock-out). DNA\/RNA epigenetic modifications and injured S3 proximal tubule cells were identified in the vitamin C\u2013deficient kidneys using whole-genome bisulfite sequencing, methylated RNA immunoprecipitation sequencing, and single-cell RNA sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Integrated evidence suggested that epigenetic modifications affected the proximal tubule cells and fenestrated endothelial cells, leading to tubule injury and hypoxia through transcriptional regulation. Strikingly, loss of DNA hydroxymethylation and DNA hypermethylation in vitamin C\u2013deficient kidneys preceded the histologic sign of tubule necrosis, indicating the causality of vitamin C\u2013induced epigenetic modification in ATN. Consistently, prophylactic supplementation of an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, promoted DNA demethylation and prevented the progression of cisplatin-induced ATN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Vitamin C played a critical role in renal homeostasis and pathogenesis in a mouse model, suggesting vitamin supplementation may be an approach to lower the risk of kidney injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021070881","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T13:55:19Z","timestamp":1641304519000},"page":"531-546","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["Vitamin C Deficiency Causes Cell Type\u2013Specific Epigenetic Reprogramming and Acute Tubular Necrosis in a Mouse Model"],"prefix":"10.1681","volume":"33","author":[{"given":"Zihui","family":"Yu","sequence":"first","affiliation":[{"name":"Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, and China National Center for Bioinformation, Chinese Academy of Sciences, Beijing, China"},{"name":"University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziying","family":"Xu","sequence":"additional","affiliation":[{"name":"Capital Institute of Pediatrics, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, and China National Center for Bioinformation, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengbin","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Chinese PLA General Hospital, Beijing, China"},{"name":"National Clinical Research Center for Orthopedics, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, and China National Center for Bioinformation, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Yu","sequence":"additional","affiliation":[{"name":"Beijing Research Institute of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Hao","sequence":"additional","affiliation":[{"name":"Core Facility for Protein Research, Institute of Biophysics, Beijing, 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