American Journal of Nephrology
Original Report: Laboratory Investigation
Inhibition of Necroptosis Attenuates Kidney Inflammation and Interstitial Fibrosis Induced By Unilateral Ureteral ObstructionXiao X.a, b · Du C.a, b · Yan Z.c · Shi Y.a, b · Duan H.a, b · Ren Y.a, baDepartment of Pathology, Hebei Medical University, bHebei Key Laboratory of Kidney Diseases, and cDepartment of Nephrology, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
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Article / Publication Details
Received: March 30, 2017
Accepted: June 01, 2017
Published online: July 20, 2017
Issue release date: August 2017
Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0
ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)
For additional information: https://www.karger.com/AJN
Abstract
Background: 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). Methods: 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. Results: 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-α, interleukin-1β, and monocyte chemotactic protein-1 was markedly attenuated by Nec-1. Furthermore, Nec-1 treatment also significantly reduced TGF-β and α-smooth muscle actin, indicating lesser renal interstitial fibrosis. Conclusion: 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.
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Article / Publication Details
Received: March 30, 2017
Accepted: June 01, 2017
Published online: July 20, 2017
Issue release date: August 2017
Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0
ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)
For additional information: https://www.karger.com/AJN
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