{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:22:02Z","timestamp":1789453322801,"version":"build-2803163510"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T00:00:00Z","timestamp":1502064000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T00:00:00Z","timestamp":1502064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an\u00a0inherited disorder that causes progressive kidney damage and renal failure. Mutations in the <jats:italic>UMOD<\/jats:italic> gene, encoding uromodulin, lead to ADTKD-<jats:italic>UMOD<\/jats:italic> related. Uromodulin is a GPI-anchored protein exclusively produced by epithelial cells of the thick ascending limb of Henle\u2019s loop. It is released in the tubular lumen after proteolytic cleavage and represents the most abundant protein in human urine in physiological condition. We previously generated and characterized a transgenic mouse model expressing mutant uromodulin (Tg<jats:sup>\n                           <jats:italic>Umod<\/jats:italic>C147W<\/jats:sup>) that recapitulates the main features of ATDKD-<jats:italic>UMOD<\/jats:italic>. While several studies clearly demonstrated that mutated uromodulin accumulates in endoplasmic reticulum, the mechanisms that lead to renal damage are not fully understood. In our work, we used kidney transcriptional profiling to identify early events of pathogenesis in the kidneys of Tg<jats:sup>\n                           <jats:italic>Umod<\/jats:italic>C147W<\/jats:sup> mice. Our results demonstrate up-regulation of inflammation and fibrosis and down-regulation of lipid metabolism in young Tg<jats:sup>\n                           <jats:italic>Umod<\/jats:italic>C147W<\/jats:sup> mice, before any functional or histological evidence of kidney damage. We also show that pro-inflammatory signals precede fibrosis onset and are already present in the first week after birth. Early induction of inflammation is likely relevant for ADTKD-<jats:italic>UMOD<\/jats:italic> pathogenesis and related pathways can be envisaged as possible novel targets for therapeutic intervention.<\/jats:p>","DOI":"10.1038\/s41598-017-07804-6","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T08:13:43Z","timestamp":1501575223000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Early involvement of cellular stress and inflammatory signals in the pathogenesis of tubulointerstitial kidney disease due to UMOD mutations"],"prefix":"10.1038","volume":"7","author":[{"given":"Matteo","family":"Trudu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Schaeffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Riba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Ikehata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Brambilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiorgio","family":"Messa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Martinelli-Boneschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Rastaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0544-7042","authenticated-orcid":false,"given":"Luca","family":"Rampoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,7]]},"reference":[{"key":"7804_CR1","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/ki.2015.28","volume":"88","author":"K-U Eckardt","year":"2015","unstructured":"Eckardt, K.-U. et al. 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