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Conference Paper: BMP7 reduces tubular inflammation and oxidative stress in diabetic nephropathy

TitleBMP7 reduces tubular inflammation and oxidative stress in diabetic nephropathy
Authors
KeywordsMedical sciences
Urology and nephrology
Issue Date2014
PublisherAmerican Society of Nephrology. The Journal's web site is located at https://www.asn-online.org/education/kidneyweek/archives/
Citation
The 2014 Annual Meeting and Scientific Exposition of the American Society of Nephrology (Kidney Week 2014), Philadelphia, PA., 11–16 November 2014. In JASN Abstract Supplement, 2014, p. 216A, abstract no. TH-PO478 How to Cite?
AbstractBACKGROUND: Bone morphogenetic protein-7 (BMP7) has been reported to confer renoprotective effects in acute and chronic kidney disease models, but its potential role in type 2 diabetic nephropathy remains unknown. METHODS: Primary human proximal tubular epithelial cells (PTECs) were growth-arrested and exposed to glycated human serum albumin (AGEs) with or without BMP7. Nine-week-old db/db mice and their db/m littermates underwent uninephrectomy (Unx) or sham operation, and received BMP7 (300 µg/kg body weight) or vehicle intraperitoneally every other day for 8 weeks before sacrifice. RESULTS: In cultured human PTECs, exposure to AGEs induced overexpression of ICAM1, MCP1, IL-8 and IL-6, involving activation of p44/42 and p38 MAPK signaling. BMP7 dose-dependently attenuated AGE-induced upregulation of ICAM1, MCP1, IL-8 and IL-6 at both mRNA and protein levels. Moreover, BMP7 suppressed AGE-induced p38 and p44/42 MAPK phosphorylation and reactive oxygen species production in PTECs. Compared with vehicle control, Unx db/db mice treated with BMP7 for 8 weeks had significantly lower urinary albumin-to-creatinine ratio (3,549±816.2 µg/mg versus 8,612±2,037 µg/mg, p=0.036), BUN (33.26±1.09 mg/dL versus 37.49±0.89 mg/dL, p=0.006), and renal cortical expression of ICAM1 and MCP1 at both gene and protein levels. In addition, BMP7-treated animals had significantly less severe tubular damage, interstitial inflammatory cell infiltration, renal cortical p38 and p44/42 phosphorylation, and lipid peroxidation. CONCLUSIONS: BMP7 attenuates tubular pro-inflammatory responses in diabetic kidney disease by suppressing oxidative stress and multiple proinflammatory signaling pathways including p38 and p44/42 MAPK. Its potential application as a therapeutic molecule in diabetic nephropathy warrants further investigation. This study is supported by a General Research Fund of the Research Grants Council (Grant number: HKU7770/09M) of Hong Kong, and the National Basic Research Program of China 973 program no. 2012CB517600 (no. 2012CB517606). Funding: Government Support - Non-U.S.
DescriptionThursday Poster - Diabetes Mellitus and Obesity: Basic/Experimental - 1: no. TH-PO478
Persistent Identifierhttp://hdl.handle.net/10722/214876
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorLi, R-
dc.contributor.authorYiu, WH-
dc.contributor.authorWu, H-
dc.contributor.authorWong, DWL-
dc.contributor.authorChan, LYY-
dc.contributor.authorLin, M-
dc.contributor.authorLeung, JCK-
dc.contributor.authorLai, KN-
dc.contributor.authorTang, SCW-
dc.date.accessioned2015-08-21T12:01:20Z-
dc.date.available2015-08-21T12:01:20Z-
dc.date.issued2014-
dc.identifier.citationThe 2014 Annual Meeting and Scientific Exposition of the American Society of Nephrology (Kidney Week 2014), Philadelphia, PA., 11–16 November 2014. In JASN Abstract Supplement, 2014, p. 216A, abstract no. TH-PO478-
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/214876-
dc.descriptionThursday Poster - Diabetes Mellitus and Obesity: Basic/Experimental - 1: no. TH-PO478-
dc.description.abstractBACKGROUND: Bone morphogenetic protein-7 (BMP7) has been reported to confer renoprotective effects in acute and chronic kidney disease models, but its potential role in type 2 diabetic nephropathy remains unknown. METHODS: Primary human proximal tubular epithelial cells (PTECs) were growth-arrested and exposed to glycated human serum albumin (AGEs) with or without BMP7. Nine-week-old db/db mice and their db/m littermates underwent uninephrectomy (Unx) or sham operation, and received BMP7 (300 µg/kg body weight) or vehicle intraperitoneally every other day for 8 weeks before sacrifice. RESULTS: In cultured human PTECs, exposure to AGEs induced overexpression of ICAM1, MCP1, IL-8 and IL-6, involving activation of p44/42 and p38 MAPK signaling. BMP7 dose-dependently attenuated AGE-induced upregulation of ICAM1, MCP1, IL-8 and IL-6 at both mRNA and protein levels. Moreover, BMP7 suppressed AGE-induced p38 and p44/42 MAPK phosphorylation and reactive oxygen species production in PTECs. Compared with vehicle control, Unx db/db mice treated with BMP7 for 8 weeks had significantly lower urinary albumin-to-creatinine ratio (3,549±816.2 µg/mg versus 8,612±2,037 µg/mg, p=0.036), BUN (33.26±1.09 mg/dL versus 37.49±0.89 mg/dL, p=0.006), and renal cortical expression of ICAM1 and MCP1 at both gene and protein levels. In addition, BMP7-treated animals had significantly less severe tubular damage, interstitial inflammatory cell infiltration, renal cortical p38 and p44/42 phosphorylation, and lipid peroxidation. CONCLUSIONS: BMP7 attenuates tubular pro-inflammatory responses in diabetic kidney disease by suppressing oxidative stress and multiple proinflammatory signaling pathways including p38 and p44/42 MAPK. Its potential application as a therapeutic molecule in diabetic nephropathy warrants further investigation. This study is supported by a General Research Fund of the Research Grants Council (Grant number: HKU7770/09M) of Hong Kong, and the National Basic Research Program of China 973 program no. 2012CB517600 (no. 2012CB517606). Funding: Government Support - Non-U.S.-
dc.languageeng-
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at https://www.asn-online.org/education/kidneyweek/archives/-
dc.relation.ispartofJournal of the American Society of Nephrology-
dc.subjectMedical sciences-
dc.subjectUrology and nephrology-
dc.titleBMP7 reduces tubular inflammation and oxidative stress in diabetic nephropathy-
dc.typeConference_Paper-
dc.identifier.emailYiu, WH: whyiu@hku.hk-
dc.identifier.emailWu, H: haojiawu@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.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros248371-
dc.identifier.spage216A, abstract no. TH-PO478-
dc.identifier.epage216A, abstract no. TH-PO478-
dc.publisher.placeUnited States-

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