{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:56:37Z","timestamp":1778633797221,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC3406705"],"award-info":[{"award-number":["2024YFC3406705"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC3406700"],"award-info":[{"award-number":["2024YFC3406700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tubular atrophy and interstitial fibrosis are basic renal pathological changes in autosomal dominant tubulointerstitial kidney disease (ADTKD). Reduced secretion or abnormal structure of uromodulin (UMOD) are recognised pathogenic factors of ADTKD. Studies show uromodulin binds complement factor H (cFH), enhancing its ability to inhibit complement activation. Overactivation of the complement system contributes to tubulointerstitial injury. Therefore, exploring the UMOD\u2013tubulointerstitial fibrosis link may aid in the development of treatment for ADTKD\u2010UMOD. Immunofluorescence staining detected complement deposition in patients' kidneys. Uromodulin's binding affinity for cFH was assessed using microthermophoresis. The effect of this binding on cFH function was analysed using C3b degradation and erythrocyte hemolysis tests. Recombinant wild\u2010type and mutant uromodulin proteins were expressed and tested using the aforementioned methods. Complement factor B was detected in the kidneys of patients with ADTKD\u2010UMOD. Patient\u2010derived uromodulin showed reduced binding to cFH and decreased capacity to assist in C3b cleavage and hemolysis inhibition. Recombinant wild\u2010type uromodulin significantly enhanced C3b cleavage (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and inhibited hemolysis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). Uromodulin mutants showed reduced binding to cFH and limited ability to promote C3b degradation, with no significant hemolysis inhibition. Impaired interactions between mutants and cFH may lead to insufficient inhibition of complement activity, triggering tubulointerstitial fibrosis.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71025","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T08:12:03Z","timestamp":1768378323000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mutations in\n                    <scp>UMOD<\/scp>\n                    Contribute to the Pathogenesis of\n                    <scp>ADTKD<\/scp>\n                    \u2010\n                    <scp>UMOD<\/scp>\n                    by Influencing the Function of Complement Factor H"],"prefix":"10.1111","volume":"30","author":[{"given":"Qiuyu","family":"Xie","sequence":"first","affiliation":[{"name":"Renal Division Peking University First Hospital  Beijing China"},{"name":"Institute of Nephrology Peking University  Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China  Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lufeng","family":"Bai","sequence":"additional","affiliation":[{"name":"Renal Division Peking University First Hospital  Beijing China"},{"name":"Institute of Nephrology Peking University  Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China  Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunjing","family":"Gong","sequence":"additional","affiliation":[{"name":"Renal Division Peking University First Hospital  Beijing China"},{"name":"Institute of Nephrology Peking University  Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China  Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Hu","sequence":"additional","affiliation":[{"name":"Renal Division Peking University First Hospital  Beijing China"},{"name":"Institute of Nephrology Peking University  Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China  Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China  Beijing China"},{"name":"Research Units of Diagnosis and Treatment of Immune\u2010Mediated Kidney Diseases Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-3106","authenticated-orcid":false,"given":"Yuqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Renal Division Peking University First Hospital  Beijing China"},{"name":"Institute of Nephrology Peking University  Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China  Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China  Beijing China"},{"name":"Research Units of Diagnosis and Treatment of Immune\u2010Mediated Kidney Diseases Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2025.05.015"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.134"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.28"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2011.08.014"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq205"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100854.2006.00481.x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2005050461"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.asn.0000092147.83480.b5"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175970"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp235"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3498215"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101711.2000.t01\u20103\u2010.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440\u20101711.2002.01125.x"},{"issue":"3","key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.4049\/jimmunol.143.3.939","article-title":"IL\u20102, a Lectin With Specificity for High Mannose Glycopeptides","volume":"143","author":"Sherblom A. 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