File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: BMP7 reduces inflammation and oxidative stress in diabetic tubulopathy

TitleBMP7 reduces inflammation and oxidative stress in diabetic tubulopathy
Authors
KeywordsAdvanced glycation end-product
Db/db mice
Diabetes mellitus
Renal tubular cell
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
2023 Impact Factor: 6.7
2023 SCImago Journal Rankings: 1.565
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.subjectAdvanced glycation end-product-
dc.subjectDb/db mice-
dc.subjectDiabetes mellitus-
dc.subjectRenal tubular cell-
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-
dc.identifier.issnl0143-5221-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats