{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T20:51:27Z","timestamp":1782420687234,"version":"3.54.5"},"reference-count":32,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;\/i&gt;&lt;\/b&gt; Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1\/RIP3\/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury. It was also aimed at evaluating the effect of Nec-1 in renal fibrosis induced by unilateral ureteral obstruction (UUO). &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Renal histology, immunohistochemistry, western blot, and real-time polymerase chain reaction were performed using UUO C57BL\/6J mice model. Moreover, we tested whether Nec-1 was renal-protective in the interstitial fibrosis kidney. Mice were exposed to UUO and injected intraperitoneal with Nec-1 or vehicle. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; The levels of RIP1\/RIP3\/MLKL protein and mRNA were increased in the obstructed kidneys 7 days after UUO; this was accompanied by changes in renal pathological lesions. Renal histological examination showed lesser renal damage in Nec-1-treated UUO mice. Renal inflammation, assessed by tumor necrosis factor-\u03b1, interleukin-1\u03b2, and monocyte chemotactic protein-1 was markedly attenuated by Nec-1. Furthermore, Nec-1 treatment also significantly reduced TGF-\u03b2 and \u03b1-smooth muscle actin, indicating lesser renal interstitial fibrosis. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; These findings suggest that the participation of necroptosis in UUO is partly demonstrated. And necroptosis inhibition may have a potential role in the treatment of diseases with increased inflammatory response and interstitial fibrosis in renal.<\/jats:p>","DOI":"10.1159\/000478746","type":"journal-article","created":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T21:01:33Z","timestamp":1500498093000},"page":"131-138","source":"Crossref","is-referenced-by-count":57,"title":["Inhibition of Necroptosis Attenuates Kidney Inflammation and Interstitial Fibrosis Induced By Unilateral Ureteral Obstruction"],"prefix":"10.1159","volume":"46","author":[{"given":"Xia","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhuo","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2017,7,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1310050"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.11.031"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200012109"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio711"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.151"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.450"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-012-0270-8"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S86748"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1159\/000025837"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.12.003"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014080741"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156729"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.12.012"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.109"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206937109"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu146"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201403856"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26200"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.037"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2011.149"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.021"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.03.006"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/nature10273"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.08.014"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.08.045"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137876"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.7150\/thno.9717"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2234"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305538110"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2970"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.02.024"}],"container-title":["American Journal of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/478746","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/478746","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:39:19Z","timestamp":1745426359000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000478746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,8,18]]},"published-print":{"date-parts":[[2017,8,22]]}},"URL":"https:\/\/doi.org\/10.1159\/000478746","archive":["Portico"],"relation":{},"ISSN":["0250-8095","1421-9670"],"issn-type":[{"value":"0250-8095","type":"print"},{"value":"1421-9670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}