title: Necroptosis mediated by receptor interaction protein kinase 1 and 3 aggravates chronic kidney injury of subtotal nephrectomised rats.
abstract: Necroptosis, an alternative mode of programmed cell death, has crucial pathophysiological roles in many diseases, but its effect on chronic kidney disease (CKD) is poorly understood. Therefore, we assessed necroptosis and its pathophysiological effects in a widely used remnant-kidney rat model. We found that necroptotic cell death and the highest level of receptor interaction protein kinase 1 (RIP1) and receptor interaction protein kinase 3 (RIP3), critical signalling molecules for necroptosis, appeared 8 weeks after subtotal nephrectomy (SNX) surgery. After treatment with Necrostatin-1 (Nec-1), renal function and renal pathologic changes were significantly improved; the overexpression of RIP1, RIP3, mixed lineage kinase domain-like (MLKL) and dynamin-related protein 1 (Drp1) was reduced; and necroptosis was inhibited. These results indicated that necroptosis mediated by RIP1 and RIP3 participates in the loss of renal cells of subtotal nephrectomised rats and might be one of main causes of the excessive loss of renal cells during the sustained progression of renal fibrosis.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hongwang
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: cqchw2013@sina.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Gan
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: xyf09200@126.com.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Pathology, Wannan Medical College, Wuhu, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D007093:Imidazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D007668:Kidney / Q000201:enzymology* / Q000473:pathology* / Q000601:surgery; D008297:Male; D009336:Necrosis / Q000378:metabolism / Q000473:pathology; D009392:Nephrectomy; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D007093:Imidazoles; D007211:Indoles; D017382:Reactive Oxygen Species; C507699:necrostatin-1; C000610381:MLKL protein, rat; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C586536:RIPK1 protein, rat; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C582791:Ripk3 protein, rat
keywords: Chronic kidney disease; Necroptosis; RIP1; RIP3