BMP7 reduces inflammation and oxidative stress in diabetic tubulopathy

Rui Xi Li, Wai Han Yiu, Hao Jia Wu, Dickson W.L. Wong, Loretta Y.Y. Chan, Miao Lin, Joseph C.K. Leung, Kar Neng Lai, Sydney C.W. Tang

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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. 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.

Original languageEnglish
Pages (from-to)269-280
Number of pages12
JournalClinical Science
Volume128
Issue number4
DOIs
StatePublished - 2015

Keywords

  • Advanced glycation end-product
  • Db/db mice
  • Diabetes mellitus
  • Renal tubular cell

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