title: Bone marrow mesenchymal stromal cells ameliorate angiogenesis and renal damage via promoting PI3k-Akt signaling pathway activation in vivo.
abstract: The objective of this study was to investigate the effects of the intravenous transplantation of bone marrow mesenchymal stromal cells (BM-MSCs) on the repair of glomerular endothelia and angiogenesis in rats with chronic renal failure (CRF). Furthermore, the mechanism of BM-MSCs promoting angiogenesis was explored by detection of Akt and P-Akt protein expression in rat kidney tissue.
  
  
  
  A rat model with CRF was established by adenine. Immature male Wistar rats were randomly divided into control group, model group and treatment group. Model group rats were injected with phosphate-buffered saline (PBS) via tail vein 24 h after the successful modeling, whereas the treatment group rats were injected with BM-MSCs. Eight weeks later, urine and blood were collected to assess 24-h proteinuria, serum creatinine (Scr) and blood urea nitrogen (BUN). We identified glomerular capillaries density using JG12 immunostaining. Levels of vascular endothelial growth factor (VEGF) were assayed using enzyme-linked immunosorbant assay (ELISA). We used Western blot to determine protein expression of p-Akt and Akt in renal tissues.
  
  
  
  Adenine induced chronic renal damage, as indicated by the mass proteinuria, deterioration of renal function and the histopathologic injury in tubules and interstitium. BM-MSCs signficantly increased capillary density and improved renal function and serum VEGF. Additionally, activation of Akt (i.e., P-Akt significantly increased) in the treatment group was increased obviously.
  
  
  
  BM-MSCs could alleviate the renal damages of adenine-induced CRF, reduce the excretion of proteinuria, increase the glomerular capillaries density, promote the secretion of VEGF and finally contribute to improve renal function. VEGF-induced angiogenesis is mediated through activating PI3k-Akt signaling pathway.
authors.affiliation: Department of Pediatric, Shanxi Medical University, Taiyuan, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Pathology, Shanxi Provincial Children's Hospital, Taiyuan, China.
authors.forename: Jinbing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Public Health, Shanxi Medical University, Taiyuan, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatric, Shanxi Medical University, Taiyuan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Pediatric, Shanxi Medical University, Taiyuan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Pediatric, Shanxi Medical University, Taiyuan, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Nephrology, Shanxi Provincial Children's Hospital, NO. 15, Xinmin North Street, Xinghualing District, Taiyuan City, Shanxi Province, China. Electronic address: yanjun9486@163.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cui
mesh_terms: D000225:Adenine; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000628:therapy; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017208:Rats, Wistar; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000225:Adenine
keywords: PI3K-Akt; angiogenesis; chronic renal failure; mesenchymal stromal cells; vascular endothelial growth factor