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

Abstract 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.