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

Conference Paper: Activation of protease-activated receptor 4 (PAR-4) in tubular epithelial cells contributes to diabetic nephropathy

TitleActivation of protease-activated receptor 4 (PAR-4) in tubular epithelial cells contributes to diabetic nephropathy
Authors
Issue Date2012
PublisherAmerican Society of Nephrology. The Journal's web site is located at https://www.asn-online.org/abstracts/
Citation
The 2012 Kidney Week, San Diego, CA., 30 October-4 November 2012. In Journal of the American Society of Nephrology, 2012, v. 23, p. 1036A, abstract no. PUB643 How to Cite?
AbstractBACKGROUND: Protease-Activated Receptors (PARs) have been implicated in the pathogenesis of many inflammation-associated disorders, however their roles in diabetic nephropathy (DN) have not yet been explored. Further to our findings on the up-regulation of PAR-4 expression in human renal proximal tubular epithelial cells (PTEC) in response to high glucose stimulation, herein we investigated the pro-inflammatory potential of this receptor in tubular cells and examined its expression in renal tissues of DN. METHODS: Renal biopsies from patients with proven DN were immunohistochemically examined for the expression of PAR-4. To elucidate the role of PAR-4, human PTEC were cultured with 1) selective PAR-4 activating peptide or 2) high glucose medium in the presence of PAR-4 antagonist, and the effects on the expression of pro-inflammatory genes were studied. RESULTS: High PAR-4 expression was detected in tubular cells of all DN biopsies whereas very low expression was found in normal control subjects. In vitro, PAR-4 activating peptide induced chemokine (C-C motif) ligand 2 (CCL-2) expression and to a lesser extent, interleukin 6 (IL-6) expression in PTEC in a time- and dose-dependent manner. Inhibition of PAR-4 by a specific antagonist partially suppressed high glucose-induced mitogen-activated protein kinase (MAPK) p42/p44 signaling and the subsequent CCL-2 and IL-6 production. CONCLUSIONS: Our data demonstrated an increased expression of tubular PAR-4 in human DN biopsies and an enhanced secretion of PAR-4 stimulated inflammatory cytokines from PTEC. These findings suggest a novel role for PAR-4 in mediating diabetic tubular injury.
DescriptionPublication Only: no. PUB643
Persistent Identifierhttp://hdl.handle.net/10722/186848
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorYiu, WHen_US
dc.contributor.authorLeung, JCKen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorChan, KWen_US
dc.contributor.authorLan, HYen_US
dc.contributor.authorLai, KNen_US
dc.contributor.authorTang, SCWen_US
dc.date.accessioned2013-08-20T12:21:14Z-
dc.date.available2013-08-20T12:21:14Z-
dc.date.issued2012en_US
dc.identifier.citationThe 2012 Kidney Week, San Diego, CA., 30 October-4 November 2012. In Journal of the American Society of Nephrology, 2012, v. 23, p. 1036A, abstract no. PUB643en_US
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/186848-
dc.descriptionPublication Only: no. PUB643-
dc.description.abstractBACKGROUND: Protease-Activated Receptors (PARs) have been implicated in the pathogenesis of many inflammation-associated disorders, however their roles in diabetic nephropathy (DN) have not yet been explored. Further to our findings on the up-regulation of PAR-4 expression in human renal proximal tubular epithelial cells (PTEC) in response to high glucose stimulation, herein we investigated the pro-inflammatory potential of this receptor in tubular cells and examined its expression in renal tissues of DN. METHODS: Renal biopsies from patients with proven DN were immunohistochemically examined for the expression of PAR-4. To elucidate the role of PAR-4, human PTEC were cultured with 1) selective PAR-4 activating peptide or 2) high glucose medium in the presence of PAR-4 antagonist, and the effects on the expression of pro-inflammatory genes were studied. RESULTS: High PAR-4 expression was detected in tubular cells of all DN biopsies whereas very low expression was found in normal control subjects. In vitro, PAR-4 activating peptide induced chemokine (C-C motif) ligand 2 (CCL-2) expression and to a lesser extent, interleukin 6 (IL-6) expression in PTEC in a time- and dose-dependent manner. Inhibition of PAR-4 by a specific antagonist partially suppressed high glucose-induced mitogen-activated protein kinase (MAPK) p42/p44 signaling and the subsequent CCL-2 and IL-6 production. CONCLUSIONS: Our data demonstrated an increased expression of tubular PAR-4 in human DN biopsies and an enhanced secretion of PAR-4 stimulated inflammatory cytokines from PTEC. These findings suggest a novel role for PAR-4 in mediating diabetic tubular injury.-
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.titleActivation of protease-activated receptor 4 (PAR-4) in tubular epithelial cells contributes to diabetic nephropathyen_US
dc.typeConference_Paperen_US
dc.identifier.emailYiu, WH: whyiu@hku.hken_US
dc.identifier.emailLeung, JCK: jckleung@hku.hken_US
dc.identifier.emailChan, LYY: yychanb@hku.hken_US
dc.identifier.emailChan, KW: hrmtckw@hku.hken_US
dc.identifier.emailLan, HY: hylan@hku.hken_US
dc.identifier.emailLai, KN: knlai@hku.hken_US
dc.identifier.emailTang, SCW: scwtang@hku.hken_US
dc.identifier.authorityLeung, JCK=rp00448en_US
dc.identifier.authorityChan, KW=rp00330en_US
dc.identifier.authorityLai, KN=rp00324en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros220823en_US
dc.identifier.volume23en_US
dc.identifier.spage1036A, abstract no. PUB643en_US
dc.identifier.epage1036A, abstract no. PUB643en_US
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats