Objectives: The aim of this study was to investigate the effect of bone mesenchymal stem cell (BMSC) conditioned medium (CM) and Bone morphogenetic protein-4 (BMP-4) on the generation of astrocytes during the process of NSCs differentiation.
Design: Neural stem cells (NSCs) were grown under different culture conditions.
Setting: The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Outcome Measures: The study consisted of four groups: NSCs cultured under control conditions (group 1) or with the addition of BMSC-CM (group 2);(BMP-4) (group 3) or both (group 4).The expression of glial fibrillary acidic protein (GFAP) was detected by immunocytochemical staining and Western blotting.
Results: The expression of GFAP was higher in Group3 and lower in Group 2 compared to that in Group 1. The expression of GFAP in Group 4 was intermediate between that of Group 2 and Group 3.
Conclusions: These results suggest that BMSC-CM can decrease the generation of astrocytes and that the inhibition of the (BMP-4) /Smad1/5/8 signaling pathway may be the underlying mechanism. This phenomenon may be mediated by increasing the expression of Smad6. 相似文献
Accumulation of extracellular matrix derived from glomerular mesangial cells is an early feature of diabetic nephropathy. Ca2+ signals mediated by store–operated Ca2+ channels regulate protein production in a variety of cell types. The aim of this study was to determine the effect of store–operated Ca2+ channels in mesangial cells on extracellular matrix protein expression. In cultured human mesangial cells, activation of store–operated Ca2+ channels by thapsigargin significantly decreased fibronectin protein expression and collagen IV mRNA expression in a dose-dependent manner. Conversely, inhibition of the channels by 2-aminoethyl diphenylborinate significantly increased the expression of fibronectin and collagen IV. Similarly, overexpression of stromal interacting molecule 1 reduced, but knockdown of calcium release–activated calcium channel protein 1 (Orai1) increased fibronectin protein expression. Furthermore, 2-aminoethyl diphenylborinate significantly augmented angiotensin II–induced fibronectin protein expression, whereas thapsigargin abrogated high glucose– and TGF-β1–stimulated matrix protein expression. In vivo knockdown of Orai1 in mesangial cells of mice using a targeted nanoparticle siRNA delivery system resulted in increased expression of glomerular fibronectin and collagen IV, and mice showed significant mesangial expansion compared with controls. Similarly, in vivo knockdown of stromal interacting molecule 1 in mesangial cells by recombinant adeno–associated virus–encoded shRNA markedly increased collagen IV protein expression in renal cortex and caused mesangial expansion in rats. These results suggest that store–operated Ca2+ channels in mesangial cells negatively regulate extracellular matrix protein expression in the kidney, which may serve as an endogenous renoprotective mechanism in diabetes. 相似文献