Bone marrow mesenchymal stromal cells ameliorate angiogenesis and renal damage via promoting PI3k-Akt signaling pathway activation in vivo.

OBJECTIVE: 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.

MATERIAL AND METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.