File Download

There are no files associated with this item.

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

Conference Paper: Kallistatin protects against diabetic nephropathy in db/db mice by suppressing AGE-RAGE-Induced oxidative stress

TitleKallistatin protects against diabetic nephropathy in db/db mice by suppressing AGE-RAGE-Induced oxidative stress
Authors
Issue Date2015
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
The 2015 Annual Meeting and Scientific Exposition of the American Society of Nephrology (Kidney Week 2015), San Diego, CA., 3-8 November 2015. In Journal of the American Society of Nephrology, 2015, v. 26, p. 169A, abstract no. TH-PO357 How to Cite?
AbstractBACKGROUND: Kallistatin is a serine protease inhibitor that exerts anti-inflammatory Anti-apoptotic and anti-oxidative effects in regulating cellular dysfunction. As oxidative stress plays a critical role in the pathogenesis of diabetic nephropathy, we aim to investigate the effect and mechanisms of kallistatin gene transfer on diabetic renal injury in the db/db mouse model of type 2 diabetes. METHODS: Plasmid with kallistatin gene was injected into the kidney of db/db mice using ultrasound-mediated microbubble-inducible gene transfer. The therapeutic potential of kallistatin in diabetic kidney was evaluated by histopathology, renal function, oxidative and fibrotic pathways. RESULTS: Kallistatin expression was induced in tubules of kidney after gene transfer compared with mice treated with empty plasmid. In db/db mice, kallistatin overexpression reduced serum creatinine and BUN levels, ameliorated glomerulosclerosis and tubulointerstitial injury and attenuated renal fibrosis by inhibiting TGF-β signaling and the downstream plasminogen activator inhibitor-1 and type IV collagen expression. Furthermore, kallistatin gene transfer significantly attenuated elevated oxidative stress in db/db mice as evidenced by suppressed levels of Nox4 and the oxidative marker (8-OHdG and MDA) in diabetic renal tissue. Finally, kallistatin inhibited expression of RAGE in both diabetic kidney and AGE-stimulated cultured proximal tubular epithelial cells, reflecting an anti-oxidative mechanism via AGE/RAGE axis. CONCLUSIONS: Our results suggest a renoprotective role of kallistatin against progression of diabetic nephropathy via anti-oxidative properties. Kallistatin reduced AGE-RAGE induced Nox4 expression, leading to suppression of oxidative stress and TGF-β-mediated renal fibrosis. Funding: Research Grants Council of Hong Kong (GRF grant number 7796/11M) and the National Basic Research Program of China 973 program no. 2012CB517600 (no 2012CB517606).
DescriptionThursday Poster - Diabetes Mellitus and Obesity: Basic-Experimental - 1: no. TH-PO357
Persistent Identifierhttp://hdl.handle.net/10722/229847
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorYiu, WH-
dc.contributor.authorWong, WLD-
dc.contributor.authorWu, H-
dc.contributor.authorLi, R-
dc.contributor.authorChan, LYY-
dc.contributor.authorLeung, JCK-
dc.contributor.authorLan, HY-
dc.contributor.authorLai, KN-
dc.contributor.authorTang, SCW-
dc.date.accessioned2016-08-23T14:13:36Z-
dc.date.available2016-08-23T14:13:36Z-
dc.date.issued2015-
dc.identifier.citationThe 2015 Annual Meeting and Scientific Exposition of the American Society of Nephrology (Kidney Week 2015), San Diego, CA., 3-8 November 2015. In Journal of the American Society of Nephrology, 2015, v. 26, p. 169A, abstract no. TH-PO357-
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/229847-
dc.descriptionThursday Poster - Diabetes Mellitus and Obesity: Basic-Experimental - 1: no. TH-PO357-
dc.description.abstractBACKGROUND: Kallistatin is a serine protease inhibitor that exerts anti-inflammatory Anti-apoptotic and anti-oxidative effects in regulating cellular dysfunction. As oxidative stress plays a critical role in the pathogenesis of diabetic nephropathy, we aim to investigate the effect and mechanisms of kallistatin gene transfer on diabetic renal injury in the db/db mouse model of type 2 diabetes. METHODS: Plasmid with kallistatin gene was injected into the kidney of db/db mice using ultrasound-mediated microbubble-inducible gene transfer. The therapeutic potential of kallistatin in diabetic kidney was evaluated by histopathology, renal function, oxidative and fibrotic pathways. RESULTS: Kallistatin expression was induced in tubules of kidney after gene transfer compared with mice treated with empty plasmid. In db/db mice, kallistatin overexpression reduced serum creatinine and BUN levels, ameliorated glomerulosclerosis and tubulointerstitial injury and attenuated renal fibrosis by inhibiting TGF-β signaling and the downstream plasminogen activator inhibitor-1 and type IV collagen expression. Furthermore, kallistatin gene transfer significantly attenuated elevated oxidative stress in db/db mice as evidenced by suppressed levels of Nox4 and the oxidative marker (8-OHdG and MDA) in diabetic renal tissue. Finally, kallistatin inhibited expression of RAGE in both diabetic kidney and AGE-stimulated cultured proximal tubular epithelial cells, reflecting an anti-oxidative mechanism via AGE/RAGE axis. CONCLUSIONS: Our results suggest a renoprotective role of kallistatin against progression of diabetic nephropathy via anti-oxidative properties. Kallistatin reduced AGE-RAGE induced Nox4 expression, leading to suppression of oxidative stress and TGF-β-mediated renal fibrosis. Funding: Research Grants Council of Hong Kong (GRF grant number 7796/11M) and the National Basic Research Program of China 973 program no. 2012CB517600 (no 2012CB517606).-
dc.languageeng-
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org-
dc.relation.ispartofJournal of the American Society of Nephrology-
dc.titleKallistatin protects against diabetic nephropathy in db/db mice by suppressing AGE-RAGE-Induced oxidative stress-
dc.typeConference_Paper-
dc.identifier.emailYiu, WH: whyiu@hku.hk-
dc.identifier.emailChan, LYY: yychanb@hku.hk-
dc.identifier.emailLeung, JCK: jckleung@hku.hk-
dc.identifier.emailLai, KN: knlai@hku.hk-
dc.identifier.emailTang, SCW: scwtang@hku.hk-
dc.identifier.authorityLeung, JCK=rp00448-
dc.identifier.authorityLai, KN=rp00324-
dc.identifier.authorityTang, SCW=rp00480-
dc.identifier.hkuros262113-
dc.identifier.volume26-
dc.identifier.spage169A, abstract no. TH-PO357-
dc.identifier.epage169A, abstract no. TH-PO357-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats