title: Mesenchymal stem cells ameliorate podocyte injury and proteinuria in a type 1 diabetic nephropathy rat model.
abstract: Mesenchymal stem cells (MSC) attenuate albuminuria and preserve normal renal histology in diabetic mice. However, the effects of MSC on glomerular podocyte injury remain uncertain. The aim of this study was to evaluate the effects of MSC on podocyte injury in streptozotocin (STZ)-induced diabetic rats. Thirty days after diabetes induction by STZ injection (65 mg/kg, intraperitoneally) in Sprague-Dawley rats, the diabetic rats received medium or 2 × 10(6) enhanced green fluorescent protein-labeled MSC via the renal artery. In vivo tracking of MSC was followed by immunofluorescence analysis. Diabetes-related physical and biochemical parameters were measured on day 60 after the MSC infusion. The expression of podocyte markers (nephrin and podocin), podocyte survival factors (VEGF and BMP-7), and the ultrastructural pathology of podocytes were also assessed. MSC were only detected in the glomeruli from the left kidney receiving MSC infusion. Compared with medium-treated diabetic rats, rats treated with MSC showed a suppressed increase in kidney weight, kidney to body weight index, creatinine clearance rate, and urinary albumin to creatinine ratio; however, the treatment had no effect on blood glucose or body weight levels. Furthermore, the MSC treatment reduced the loss of podocytes, effacement of foot processes, widening of foot processes, thickening of glomerular basal membrane (GBM), and loss of glomerular nephrin and podocin. Most important, MSC-injected kidneys expressed higher levels of BMP-7 but not of VEGF. Our results clearly demonstrated that intra-arterial administration of MSC prevented the development of albuminuria as well as any damage to or loss of podocytes, though there was no improvement in blood sugar levels. The protective effects of MSC may be mediated in part by increasing BMP-7 secretion.
authors.affiliation: Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Jinghong
authors.initials: J
authors.lastname: Zhao
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhang
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D055419:Bone Morphogenetic Protein 7; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D042461:Vascular Endothelial Growth Factor A; C113267:nephrin; C467498:vascular endothelial growth factor A, rat; D049452:Green Fluorescent Proteins; D013311:Streptozocin