File Download
  Links for fulltext
     (May Require Subscription)
  • Find via Find It@HKUL
Supplementary

Conference Paper: Ac-SDKP reduces proinflammatory response in PTEC during pathogenic albumin load

TitleAc-SDKP reduces proinflammatory response in PTEC during pathogenic albumin load
Authors
Issue Date2010
PublisherAmerican Society of Nephrology. The Journal's web site is located at https://www.asn-online.org/abstracts/
Citation
Renal Week 2010, Denver, CO., 16-21 November 2010. In Journal of the American Society of Nephrology, 2010, v. 21, p. 279A, abstract no. TH-PO733 How to Cite?
AbstractBACKGROUND: Tubulointerstitial injury in diabetic nephropathy (DN) is an important factor in disease progression. Kidney injury molecule-1 (KIM-1) is expressed by proximal tubular epithelial cell (PTEC) and released upon kidney injury. In this study, we examine the kinetics and mechanism of KIM-1 release in PTEC under the activation by different mediators of DN, including human serum albumin (HSA), advanced glycation endproducts (AGE) and glucose. METHODS: The kinetics of KIM-1 and MMP-3 release by PTEC under the activation with HSA, AGE and glucose; was determined by RT-PCR and ELISA. The activation profiles of major signaling pathways in PTEC cultured with HSA, AGE and glucose, were identified by PCR array. Based on these array data, blockade experiments with various signaling inhibitors were designed to examine their regulatory roles on KIM-1 release. RESULTS: We have shown that HSA induce KIM-1 shedding in PTEC by MMP-3. We further addressed the potency and kinetics of AGE- and glucose-mediated KIM-1 shedding in PTEC as compared to that of HSA. Prompt shedding of KIM-1 was observed in PTEC cultured 4 h with HSA and AGE, but not with glucose. Long term culturing PTEC for 3 days with AGE exhibited sustained release of KIM-1 and this is not observed for HSA. In all experiments, glucose did not induce KIM-1 release by PTEC. HSA and AGE activated the ERK and NF-kB pathways in PTEC. The Jak-Stat pathway was activated by AGE but not by HSA. Incubation of PTEC with diphenylene iodonium, but not pyrrolidine dithiocarbamate, P98059 or fludarabine, blocked the short term release of KIM-1 mediated by HSA or AGE. Interestingly, fludarabine but not diphenylene iodonium, pyrrolidine dithiocarbamate or PD98059, diminished the long term KIM-1 release by PTEC cultured with AGE. CONCLUSIONS: Our data suggest that KIM-1 release in PTEC was differentially upregulated by HSA and AGE. The short term KIM-1 release was mediated by the reactive oxygen species while Jak-Stat pathway controls the long-term KIM-1 release mediated by AGE.
DescriptionThursday Poster Presentation - Immunology, Pathology: Basic/Experimental Inflammation: no. TH-PO733
Persistent Identifierhttp://hdl.handle.net/10722/137786
ISSN
2014 Impact Factor: 9.343

 

DC FieldValueLanguage
dc.contributor.authorAu, WSen_US
dc.contributor.authorChan, Gen_US
dc.contributor.authorLeung, JCKen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorLan, HYen_US
dc.contributor.authorLai, KNen_US
dc.contributor.authorTang, SCWen_US
dc.date.accessioned2011-08-26T14:33:23Z-
dc.date.available2011-08-26T14:33:23Z-
dc.date.issued2010en_US
dc.identifier.citationRenal Week 2010, Denver, CO., 16-21 November 2010. In Journal of the American Society of Nephrology, 2010, v. 21, p. 279A, abstract no. TH-PO733en_US
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/137786-
dc.descriptionThursday Poster Presentation - Immunology, Pathology: Basic/Experimental Inflammation: no. TH-PO733-
dc.description.abstractBACKGROUND: Tubulointerstitial injury in diabetic nephropathy (DN) is an important factor in disease progression. Kidney injury molecule-1 (KIM-1) is expressed by proximal tubular epithelial cell (PTEC) and released upon kidney injury. In this study, we examine the kinetics and mechanism of KIM-1 release in PTEC under the activation by different mediators of DN, including human serum albumin (HSA), advanced glycation endproducts (AGE) and glucose. METHODS: The kinetics of KIM-1 and MMP-3 release by PTEC under the activation with HSA, AGE and glucose; was determined by RT-PCR and ELISA. The activation profiles of major signaling pathways in PTEC cultured with HSA, AGE and glucose, were identified by PCR array. Based on these array data, blockade experiments with various signaling inhibitors were designed to examine their regulatory roles on KIM-1 release. RESULTS: We have shown that HSA induce KIM-1 shedding in PTEC by MMP-3. We further addressed the potency and kinetics of AGE- and glucose-mediated KIM-1 shedding in PTEC as compared to that of HSA. Prompt shedding of KIM-1 was observed in PTEC cultured 4 h with HSA and AGE, but not with glucose. Long term culturing PTEC for 3 days with AGE exhibited sustained release of KIM-1 and this is not observed for HSA. In all experiments, glucose did not induce KIM-1 release by PTEC. HSA and AGE activated the ERK and NF-kB pathways in PTEC. The Jak-Stat pathway was activated by AGE but not by HSA. Incubation of PTEC with diphenylene iodonium, but not pyrrolidine dithiocarbamate, P98059 or fludarabine, blocked the short term release of KIM-1 mediated by HSA or AGE. Interestingly, fludarabine but not diphenylene iodonium, pyrrolidine dithiocarbamate or PD98059, diminished the long term KIM-1 release by PTEC cultured with AGE. CONCLUSIONS: Our data suggest that KIM-1 release in PTEC was differentially upregulated by HSA and AGE. The short term KIM-1 release was mediated by the reactive oxygen species while Jak-Stat pathway controls the long-term KIM-1 release mediated by AGE.-
dc.languageengen_US
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at https://www.asn-online.org/abstracts/-
dc.relation.ispartofJASN Abstract Supplementen_US
dc.titleAc-SDKP reduces proinflammatory response in PTEC during pathogenic albumin loaden_US
dc.typeConference_Paperen_US
dc.identifier.emailLeung, JCK: jckleung@hku.hken_US
dc.identifier.emailChan, LYY: yychanb@hku.hken_US
dc.identifier.emailLan, HY: hylan@hku.hken_US
dc.identifier.emailLai, KN: knlai@hku.hk-
dc.identifier.emailTang, SCW: scwtang@hku.hk-
dc.identifier.authorityLeung, JCK=rp00448en_US
dc.identifier.authorityLai, KN=rp00324en_US
dc.identifier.authorityTang, SCW=rp00480en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros190989en_US
dc.identifier.volume21en_US
dc.identifier.spage279A, abstract no. TH-PO733en_US
dc.identifier.epage279A, abstract no. TH-PO733en_US
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats