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Article: BMP7 reduces inflammation and oxidative stress in diabetic tubulopathy

TitleBMP7 reduces inflammation and oxidative stress in diabetic tubulopathy
Authors
Issue Date2015
PublisherPortland Press Ltd. The Journal's web site is located at http://www.clinsci.org/
Citation
Clinical Science, 2015, v. 128 n. 4, p. 269-280 How to Cite?
AbstractBone 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. In cultured human proximal tubular epithelial cells (PTECs), exposure to advanced glycation end-products (AGEs) induced overexpression of intercellular adhesion molecule 1 (ICAM1), monocyte chemoattractant protein 1 (MCP1), interleukin 8 (IL-8) and interleukin 6 (IL-6), involving activation of p44/42 and p38 mitogen-activated protein kinase (MAPK) signalling. BMP7 dose-dependently attenuated AGE-induced up-regulation 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, uninephrectomized db/db mice treated with BMP7 for 8 weeks had significantly lower urinary albumin-to-creatinine ratio (3549±816.2 μg/mg compared with 8612±2037 μg/mg, P=0.036), blood urea nitrogen (33.26±1.09 mg/dl compared with 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. Our results demonstrate that BMP7 attenuates tubular pro-inflammatory responses in diabetic kidney disease by suppressing oxidative stress and multiple inflammatory signalling pathways including p38 and p44/42 MAPK. Its potential application as a therapeutic molecule in diabetic nephropathy warrants further investigation.
Persistent Identifierhttp://hdl.handle.net/10722/214358
ISSN
2015 Impact Factor: 4.996
2015 SCImago Journal Rankings: 2.427
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, RX-
dc.contributor.authorYiu, WH-
dc.contributor.authorWu, HJ-
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.accessioned2015-08-21T11:18:31Z-
dc.date.available2015-08-21T11:18:31Z-
dc.date.issued2015-
dc.identifier.citationClinical Science, 2015, v. 128 n. 4, p. 269-280-
dc.identifier.issn0143-5221-
dc.identifier.urihttp://hdl.handle.net/10722/214358-
dc.description.abstractBone 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. In cultured human proximal tubular epithelial cells (PTECs), exposure to advanced glycation end-products (AGEs) induced overexpression of intercellular adhesion molecule 1 (ICAM1), monocyte chemoattractant protein 1 (MCP1), interleukin 8 (IL-8) and interleukin 6 (IL-6), involving activation of p44/42 and p38 mitogen-activated protein kinase (MAPK) signalling. BMP7 dose-dependently attenuated AGE-induced up-regulation 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, uninephrectomized db/db mice treated with BMP7 for 8 weeks had significantly lower urinary albumin-to-creatinine ratio (3549±816.2 μg/mg compared with 8612±2037 μg/mg, P=0.036), blood urea nitrogen (33.26±1.09 mg/dl compared with 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. Our results demonstrate that BMP7 attenuates tubular pro-inflammatory responses in diabetic kidney disease by suppressing oxidative stress and multiple inflammatory signalling pathways including p38 and p44/42 MAPK. Its potential application as a therapeutic molecule in diabetic nephropathy warrants further investigation.-
dc.languageeng-
dc.publisherPortland Press Ltd. The Journal's web site is located at http://www.clinsci.org/-
dc.relation.ispartofClinical Science-
dc.rightsThe final version of record is available at http://www.clinsci.org/content/128/4/269-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleBMP7 reduces inflammation and oxidative stress in diabetic tubulopathy-
dc.typeArticle-
dc.identifier.emailYiu, WH: whyiu@hku.hk-
dc.identifier.emailWu, HJ: 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.naturepostprint-
dc.identifier.doi10.1042/CS20140401-
dc.identifier.pmid25200314-
dc.identifier.scopuseid_2-s2.0-84926505003-
dc.identifier.hkuros248222-
dc.identifier.volume128-
dc.identifier.issue4-
dc.identifier.spage269-
dc.identifier.epage280-
dc.identifier.isiWOS:000349364500004-
dc.publisher.placeUnited Kingdom-

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