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Conference Paper: Amelioration of albuminuria and tubulointerstitial inflammation in STZ-induced diabetic TLR4-deficient mice

TitleAmelioration of albuminuria and tubulointerstitial inflammation in STZ-induced diabetic TLR4-deficient mice
Authors
Issue Date2011
PublisherAmerican Society of Nephrology. The Journal's web site is located at https://www.asn-online.org/abstracts/
Citation
Kidney Week 2011, Philadelphia, PA., 8-13 November 2011. In Journal of the American Society of Nephrology, 2011, v. 22, p. 466A, abstract no. FR-PO1522 How to Cite?
AbstractBACKGROUND: We recently showed that tubular Toll-like receptor 4 (TLR4) expression was elevated in renal biopsies of histologically proven diabetic nephropathy (DN) and correlated with interstitial macrophage infiltration and HbA1c level. But the role of TLR4 in DN remains speculative. This study aims to study the role of TLR4 by using STZ-induced diabetic TLR4-deficient mice. METHODS: TLR4-/- mice and their wild type littermates (TLR4+/+) on C57BL6 background at 10-12 weeks old underwent uninephrectomy (Unx) or sham operation, and were then rendered diabetic by intraperitoneal injections of STZ. In vitro, the effect of an anti-TLR4 neutralizing antibody on high glucose (HG)-induced human proximal tubular epithelial cell (PTEC) inflammation was examined. RESULTS: At 12 weeks of diabetes, TLR4-/- mice demonstrated significantly ameliorated albuminuria and serum creatinine independent of blood glucose levels. This functional improvement was accompanied by substantially decreased F4/80+ macrophage infiltration into the tubulointerstitium and downregulation of cortical CCL-2, ICAM-1, and IL-1beta expression. At the signaling level, tubulointerstitial phosphorylated NF-κB/p65 activation was reduced in diabetic TLR4 -/- vs WT mice. The role of tubular TLR4 was confirmed in vitro. Pretreatment of PTEC with an anti-TLR4 neutralizing antibody significantly attenuated HG-induced NF-κB nuclear translocation and the downstream CCL-2 overexpression. CONCLUSIONS: Our data suggest a pathogenic role of TLR4 in tubulointerstitial inflammation of diabetic kidney injury, and TLR4 may be a promising therapeutic target for further investigation.
DescriptionFriday Poster Presentation - Diabetic Nephropathy Basic - II: no. FR-PO1522
Persistent Identifierhttp://hdl.handle.net/10722/160326
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorLin, Men_US
dc.contributor.authorYiu, WHen_US
dc.contributor.authorWu, Hen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorLeung, JCKen_US
dc.contributor.authorLai, KNen_US
dc.contributor.authorTang, SCWen_US
dc.date.accessioned2012-08-16T06:08:02Z-
dc.date.available2012-08-16T06:08:02Z-
dc.date.issued2011en_US
dc.identifier.citationKidney Week 2011, Philadelphia, PA., 8-13 November 2011. In Journal of the American Society of Nephrology, 2011, v. 22, p. 466A, abstract no. FR-PO1522en_US
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/160326-
dc.descriptionFriday Poster Presentation - Diabetic Nephropathy Basic - II: no. FR-PO1522-
dc.description.abstractBACKGROUND: We recently showed that tubular Toll-like receptor 4 (TLR4) expression was elevated in renal biopsies of histologically proven diabetic nephropathy (DN) and correlated with interstitial macrophage infiltration and HbA1c level. But the role of TLR4 in DN remains speculative. This study aims to study the role of TLR4 by using STZ-induced diabetic TLR4-deficient mice. METHODS: TLR4-/- mice and their wild type littermates (TLR4+/+) on C57BL6 background at 10-12 weeks old underwent uninephrectomy (Unx) or sham operation, and were then rendered diabetic by intraperitoneal injections of STZ. In vitro, the effect of an anti-TLR4 neutralizing antibody on high glucose (HG)-induced human proximal tubular epithelial cell (PTEC) inflammation was examined. RESULTS: At 12 weeks of diabetes, TLR4-/- mice demonstrated significantly ameliorated albuminuria and serum creatinine independent of blood glucose levels. This functional improvement was accompanied by substantially decreased F4/80+ macrophage infiltration into the tubulointerstitium and downregulation of cortical CCL-2, ICAM-1, and IL-1beta expression. At the signaling level, tubulointerstitial phosphorylated NF-κB/p65 activation was reduced in diabetic TLR4 -/- vs WT mice. The role of tubular TLR4 was confirmed in vitro. Pretreatment of PTEC with an anti-TLR4 neutralizing antibody significantly attenuated HG-induced NF-κB nuclear translocation and the downstream CCL-2 overexpression. CONCLUSIONS: Our data suggest a pathogenic role of TLR4 in tubulointerstitial inflammation of diabetic kidney injury, and TLR4 may be a promising therapeutic target for further investigation.-
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.titleAmelioration of albuminuria and tubulointerstitial inflammation in STZ-induced diabetic TLR4-deficient miceen_US
dc.typeConference_Paperen_US
dc.identifier.emailYiu, WH: whyiu@hku.hken_US
dc.identifier.emailChan, LYY: yychanb@hkucc.hku.hken_US
dc.identifier.emailLeung, JCK: jckleung@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.authorityLai, KN=rp00324en_US
dc.identifier.authorityTang, SCW=rp00480en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros204003en_US
dc.identifier.volume22en_US
dc.identifier.spage466A, abstract no. FR-PO1522-
dc.identifier.epage466A, abstract no. FR-PO1522-
dc.publisher.placeUnited States-

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