{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T13:29:27Z","timestamp":1789824567127,"version":"4.0.1"},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Uromodulin (Umod) is the most abundant constituent of urine in humans and exclusively found in the kidney tubular epithelium. However, the specific role of Umod in renal tubulointerstitial injury is yet to be understood. The present study was conducted with aim of investigating the potential therapeutic mechanism of Umod in the regulation of renal tubulointerstitial injury. Protein expression of Umod in renal tubular epithelial cells was measured with the conduction of Western blot analysis. Enzyme\u2010linked immunosorbent assay and immunofluorescence assay\u00a0were performed to detect the complement activation products and the activation products of surface deposition. The expression of C1q, C2, C4, B factor, C3, C5, H factor, CD46, CD55, C3aR, and C5aR were determined with the use of reverse\u2010transcription quantitative polymerase chain reaction\u00a0and Western blot analyses. Subsequently, the unilateral ureteral obstruction (UUO) rat model was established. Renal tubulointerstitial injury was assessed with the application of hematoxylin\u2013eosin staining and Masson staining in rats. UUO rats and normal rats were injected with si\u2010NC or si\u2010Umod and complement inhibitor. UUO rats were observed to have serious impairment of kidney tubule, renal tubular dilation, and epithelial atrophy, with downregulated Umod and activated complement pathway. Silencing of Umod resulted in the activation of complement system while promoting interstitial fibrosis in renal tubules. Moreover, addition of complement inhibitor significantly alleviated the renal tubule injury and fibrosis. Collectively, our study suggests that silencing of Umod mediates the complement pathway, exacerbating renal tubulointerstitial injury in rats, which provides insight into the development of novel therapeutic agents for renal tubulointerstitial injury.<\/jats:p>","DOI":"10.1002\/jcp.30208","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T12:17:34Z","timestamp":1609935454000},"page":"5012-5021","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Uromodulin aggravates renal tubulointerstitial injury through activation of the complement pathway in rats"],"prefix":"10.1002","volume":"236","author":[{"given":"Li","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery Shandong Provincial Hospital Affiliated to Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoling","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4536-9402","authenticated-orcid":false,"given":"Maojing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13208"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431x20187476"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfz065"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.01.010"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2011.10.054"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.5527\/wjn.v4.i1.31"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29008-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12872"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44241-z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2012.12.033"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2013.08.001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2019.02.024"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2014.06.035"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1305"},{"key":"e_1_2_9_16_1","first-page":"23","article-title":"Tamm\u2010Horsfall protein is a potent immunomodulatory molecule and a disease biomarker in the urinary system","volume":"23","author":"Wu T. 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