nephrin and Necrosis

Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6-8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (

Topics: Animals; Apoptosis; Bone Marrow Cells; Caspase 3; Disease Models, Animal; Everolimus; Kidney Glomerulus; Male; Membrane Proteins; Necrosis; Oxidative Stress; Rats, Sprague-Dawley; Stem Cell Transplantation; Stem Cells; Thiobarbituric Acid Reactive Substances

Antibody-mediated rejection (AMR) accounts for >50% of kidney allograft loss. Donor-specific antibodies (DSA) against HLA and non-HLA antigens in the glomeruli and the tubulointerstitium cause AMR while inflammatory cytokines such as TNF. Unbiased proteomic analysis of laser-captured and microdissected glomeruli and tubulointerstitium was performed on 30 for-cause kidney biopsy specimens with early AMR, acute cellular rejection (ACR), or acute tubular necrosis (ATN).. A total of 107 of 2026 glomerular and 112 of 2399 tubulointerstitial proteins was significantly differentially expressed in AMR versus ACR; 112 of 2026 glomerular and 181 of 2399 tubulointerstitial proteins were significantly dysregulated in AMR versus ATN (. Basement membranes are often remodeled in chronic AMR. Proteomic analysis performed on laser-captured and microdissected glomeruli and tubulointerstitium identified early ECM remodeling, which may represent a new therapeutic opportunity.

Topics: Adult; Aged; Allografts; Antibodies; Basement Membrane; Biopsy; Cathepsins; Cell Line; Cysteine Endopeptidases; Extracellular Matrix; Female; Galectin 1; Gene Expression; Glutathione Transferase; Graft Rejection; Histocompatibility Antigens Class I; Humans; Kidney Glomerulus; Kidney Transplantation; Kidney Tubules; Laminin; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Membrane Proteins; Middle Aged; Necrosis; Proteomics; Receptor-Like Protein Tyrosine Phosphatases, Class 3; Tumor Necrosis Factor-alpha