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Deletion Of XIAP re...
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Liu, YongSichuan University, Peoples R China; Sichuan University, Peoples R China
(författare)
Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity
- Artikel/kapitelEngelska2017
Förlag, utgivningsår, omfång ...
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2017-03-16
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NATURE PUBLISHING GROUP,2017
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-136628
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-136628URI
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https://doi.org/10.1038/cddis.2017.70DOI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding Agencies|National Natural Science Fund of China (NSFC) [30830100, 81170439, 81470886, 81500486]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (SRF for ROCS, SEM) [20101174-4-2]
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Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Chen, Xiao-DongSichuan University, Peoples R China
(författare)
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Yu, JiangSichuan University, Peoples R China
(författare)
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Chi, Jun-LinSichuan University, Peoples R China
(författare)
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Long, Fei-WuSichuan University, Peoples R China
(författare)
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Yang, Hong-WeiSichuan University, Peoples R China
(författare)
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Chen, Ke-LingSichuan University, Peoples R China
(författare)
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Lv, Zhao-YingSichuan University, Peoples R China
(författare)
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Zhou, BinSichuan University, Peoples R China
(författare)
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Peng, Zhi-HaiShanghai Jiao Tong University, Peoples R China
(författare)
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Sun, Xiao-FengLinköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US,Sichuan University, Peoples R China(Swepub:liu)xiasu45
(författare)
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Li, YuanSichuan University, Peoples R China
(författare)
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Zhou, Zong-GuangSichuan University, Peoples R China
(författare)
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Sichuan University, Peoples R China; Sichuan University, Peoples R ChinaSichuan University, Peoples R China
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Cell Death and Disease: NATURE PUBLISHING GROUP82041-4889
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Till lärosätets databas
- Av författaren/redakt...
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Liu, Yong
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Chen, Xiao-Dong
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Yu, Jiang
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Chi, Jun-Lin
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Long, Fei-Wu
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Yang, Hong-Wei
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visa fler...
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Chen, Ke-Ling
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Lv, Zhao-Ying
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Zhou, Bin
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Peng, Zhi-Hai
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Sun, Xiao-Feng
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Li, Yuan
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Zhou, Zong-Guang
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- MEDICIN OCH HÄLSOVETENSKAP
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Cell Death and D ...
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Linköpings universitet