title: Angiotensin receptor blockade attenuates glomerulosclerosis progression by promoting VEGF expression and bone marrow-derived cells recruitment.
abstract: 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.
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital, and Department of Pharmacology, Harbin Medical University, Harbin, People’s Republic of China.
authors.forename: Shu-min
authors.initials: SM
authors.lastname: Song
authors.forename: Cen-cen
authors.initials: CC
authors.lastname: Wang
authors.forename: Si-hua
authors.initials: SH
authors.lastname: Qi
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.forename: Bao-feng
authors.initials: BF
authors.lastname: Yang
authors.forename: Takashi
authors.initials: T
authors.lastname: Oite
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007518:Isoantibodies / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D011945:Receptors, Angiotensin / Q000737:chemistry*; D013777:Tetrazoles / Q000627:therapeutic use*; D018800:Thy-1 Antigens / Q000276:immunology; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D057911:Angiotensin Receptor Antagonists; D007518:Isoantibodies; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D018800:Thy-1 Antigens; D042461:Vascular Endothelial Growth Factor A; C035678:anti-Thy antibody; C485184:enhanced green fluorescent protein; C467498:vascular endothelial growth factor A, rat; D049452:Green Fluorescent Proteins; D000068756:Valsartan; D014633:Valine