{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:13:34Z","timestamp":1790187214207,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004374","name":"Chongqing Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To investigate the role of histidine metabolism in diabetic kidney disease (DKD), we analysed histidine metabolism\u2010related genes using an integrative multi\u2010omics approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Untargeted metabolomics was performed on serum from DKD persons and healthy controls, as well as on high glucose\u2010treated and normal glucose\u2010treated HK\u20102 cells, to assess metabolic alterations. We also analysed publicly available datasets, including GEO transcriptomes, Kidney Precision Medicine Project (KPMP), Kidney Interactive Transcriptomics single\u2010cell data, the Human Protein Atlas (HPA) and Nephroseq, to examine the expression and function of histidine metabolism\u2010related genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum metabolomics confirmed alterations in histidine metabolism. Single\u2010cell analysis revealed that five histidine metabolism\u2010related genes were expressed in proximal tubular epithelial cells and significantly downregulated in DKD. Immunohistochemistry data from the HPA further demonstrated that the corresponding proteins are localized in the proximal tubule (PT). High\u2010glucose treatment suppressed histidine metabolism in HK\u20102 cells, supporting specific metabolic reprogramming. Clinical correlation analyses using Nephroseq linked the decreased expression of these genes to renal function decline. Collectively, these findings indicate that histidine metabolic disruption is associated with tubular cell dysfunction, suggesting a mechanistic contribution to DKD progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By integrating multi\u2010omics analyses, we suggest that histidine metabolic reprogramming represents a PT pathological event in DKD, providing novel mechanistic insights and potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dme.70238","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T03:45:23Z","timestamp":1775619923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrative multi\u2010omics suggests core gene dysregulation of histidine metabolism in diabetic kidney disease"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9526-8280","authenticated-orcid":false,"given":"Jiang","family":"Tan","sequence":"first","affiliation":[{"name":"College of Artificial Intelligence Medicine Chongqing Medical University  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, College of Basic Medicine Chongqing Medical University  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengning","family":"Chuan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Chongqing University Fuling Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Nephrology Chongqing University Fuling Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjun","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Science &amp; Technology Innovation Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiliang","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Artificial Intelligence Medicine Chongqing Medical University  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00115.2024"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S507171"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2020.204"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1602594"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2023.1239838"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15010184"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119134"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-2839-7"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157001"},{"issue":"6","key":"e_1_2_11_11_1","first-page":"714","article-title":"Ameliorative effects of histidine on oxidative stress, tumor necrosis factor alpha (TNF\u2010\u03b1), and renal histological alterations in streptozotocin\/nicotinamide\u2010induced type 2 diabetic rats","volume":"23","author":"Nasri M","year":"2020","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.02.010"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40200-021-00967-0"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.765873"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-023-03330-0"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1267\/ahc.20008"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0796"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0000000000000248"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep38942"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-024-01224-6"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2024.09.010"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.5527\/wjn.v4.i2.196"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103393"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1079446"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2025.05.007"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00047.2023"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.08.036"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155195"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.661185"}],"container-title":["Diabetic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.70238","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dme.70238","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.70238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:21:22Z","timestamp":1779294082000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dme.70238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/dme.70238"],"URL":"https:\/\/doi.org\/10.1111\/dme.70238","archive":["Portico"],"relation":{},"ISSN":["0742-3071","1464-5491"],"issn-type":[{"value":"0742-3071","type":"print"},{"value":"1464-5491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"2025-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70238"}}