BMP7 reduces inflammation and oxidative stress in diabetic tubulopathy

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) 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, uninephrectomized db/db mice treated with BMP7 for 8 weeks had significantly lower urinary albumin-to-creatinine ratio (3,549±816.2 μg/mg vs. 8,612±2,037 μg/mg, p=0.036), blood urea nitrogen (33.26±1.09 mg/dL vs. 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 demonstrated that BMP7 attenuates tubular pro-inflammatory responses in diabetic kidney di...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research