Journal Article

Angiotensin receptor blockade attenuates glomerulosclerosis progression by promoting VEGF expression and bone marrow-derived cells recruitment

Shu-min Song, Cen-cen Wang, Si-hua Qi, Li Xing, Bao-feng Yang, Takashi Oite and Bing Li

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 7, pages 2712-2719
Published in print July 2012 | ISSN: 0931-0509
Published online December 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr621
Angiotensin receptor blockade attenuates glomerulosclerosis progression by promoting VEGF expression and bone marrow-derived cells recruitment

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Background

Previous studies have demonstrated that angiotensin Type I receptor blockade (ARB) reduces proteinuria, reverses glomerular injury and glomerulosclerosis in rat models of diabetic nephropathy and glomerulonephritis. However, the cellular and molecular mechanisms are unclear. To investigate the role of cells of the bone marrow (BM) in glomerular repair seen during ARB administration, we induced progressive glomerulosclerosis in enhanced green fluorescent protein BM chimeric rats by a single injection of anti-Thy 1.1 monoclonal antibody, followed by unilateral nephrectomy.

Methods

Cohorts of rats received valsartan or no treatment from Week 2 to Week 8 after induction of disease. Renal function, urinary protein excretion and histological changes were examined 8 weeks after anti-Thy-1.1 monoclonal antibody injection.

Results

Valsartan administration improved renal function, reduced severity of glomerulosclrosis and markedly reduced mortality. Valsartan administration promoted regeneration of the glomerular tuft, lowered proteinuria and resulted in enhanced vascular endothelial growth factor (VEGF) expression in the cortex and glomerular tuft. In addition, valsartan promoted increased recruitment of BM-derived cells (BMDCs) many of which expressed VEGF and likely contributed directly to glomerular repair. Nearly all BMDCs recruited to the glomerulus expressed the monocyte/macrophage marker CD68.

Conclusions

In conclusion, the data shows that ARB by valsartan prevents glomerulosclerosis progression by enhancing glomerular capillary repair which is associated with the recruitment of VEGF producing ‘reparative’ monocytes and macrophages from the BM.

Keywords: ARB; bone marrow-derived cells; glomerular capillary repair; glomerulosclerosis; VEGF

Journal Article.  4510 words.  Illustrated.

Subjects: Nephrology

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