Sökning: onr:"swepub:oai:DiVA.org:liu-136628" > Deletion Of XIAP re...
Fältnamn | Indikatorer | Metadata |
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000 | 04979naa a2200469 4500 | |
001 | oai:DiVA.org:liu-136628 | |
003 | SwePub | |
008 | 170421s2017 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1366282 URI |
024 | 7 | a https://doi.org/10.1038/cddis.2017.702 DOI |
040 | a (SwePub)liu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Liu, Yongu Sichuan University, Peoples R China; Sichuan University, Peoples R China4 aut |
245 | 1 0 | a Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity |
264 | c 2017-03-16 | |
264 | 1 | b NATURE PUBLISHING GROUP,c 2017 |
338 | a electronic2 rdacarrier | |
500 | a 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] | |
520 | a 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. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng |
700 | 1 | a Chen, Xiao-Dongu Sichuan University, Peoples R China4 aut |
700 | 1 | a Yu, Jiangu Sichuan University, Peoples R China4 aut |
700 | 1 | a Chi, Jun-Linu Sichuan University, Peoples R China4 aut |
700 | 1 | a Long, Fei-Wuu Sichuan University, Peoples R China4 aut |
700 | 1 | a Yang, Hong-Weiu Sichuan University, Peoples R China4 aut |
700 | 1 | a Chen, Ke-Lingu Sichuan University, Peoples R China4 aut |
700 | 1 | a Lv, Zhao-Yingu Sichuan University, Peoples R China4 aut |
700 | 1 | a Zhou, Binu Sichuan University, Peoples R China4 aut |
700 | 1 | a Peng, Zhi-Haiu Shanghai Jiao Tong University, Peoples R China4 aut |
700 | 1 | a Sun, Xiao-Fengu Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US,Sichuan University, Peoples R China4 aut0 (Swepub:liu)xiasu45 |
700 | 1 | a Li, Yuanu Sichuan University, Peoples R China4 aut |
700 | 1 | a Zhou, Zong-Guangu Sichuan University, Peoples R China4 aut |
710 | 2 | a Sichuan University, Peoples R China; Sichuan University, Peoples R Chinab Sichuan University, Peoples R China4 org |
773 | 0 | t Cell Death and Diseased : NATURE PUBLISHING GROUPg 8q 8x 2041-4889 |
856 | 4 | u https://liu.diva-portal.org/smash/get/diva2:1089865/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 | u https://doi.org/10.1038/cddis.2017.70 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-136628 |
856 | 4 8 | u https://doi.org/10.1038/cddis.2017.70 |
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