College of Life Science, Henan Normal University , Xinxiang , Henan Province , China.
State Key Laboratory Cultivation Base for Cell Differentiation Regulation, Henan Normal University , Xinxiang , Henan Province , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3745-3757. doi: 10.1080/21691401.2019.1666862.
This study aimed to examine the effects of osteopontin (OPN) on hepatocyte growth and liver regeneration (LR). A recombinant lentivirus expressing OPN and OPN-siRNAs were used to treat BRL-3A cells, while the adenovirus expressing OPN or OPN-targeted shRNA were applied for rat primary hepatocytes. Moreover, rrOPN and OPN-Ab were added to treat BRL-3A. Next, rrOPN was administrated into rat regenerating livers. Then and assays were performed to evaluate the biological function of OPN in hepatocyte growth and LR. OPN overexpression facilitated proliferation and viability of BRL-3A cells and primary hepatocytes, while OPN silencing reversed these effects. Similarly, rrOPN stimulated cell cycle progression and viability, but OPN-Ab led to cell cycle arrest and decreased viability. OPN overexpression induced the expression of p-STAT3, p-AKT and CCND1, and OPN siRNA led to reduction of p-AKT and CCND1. Furthermore, rrOPN promoted the expression of p-STAT3 and p-AKT, while OPN-Ab and PI3K/Akt inhibitor LY294002 both inhibited the expressions of p-AKT and Bcl2. Moreover, LR rate, serum IL-6 and TNF-α, Ki-67 proportion and the phosphorylation of STAT3, AKT and p65 were augmented by rrOPN treatment. OPN promotes hepatocyte proliferation both and through STAT3 and AKT signaling pathways.
本研究旨在探讨骨桥蛋白（OPN）对肝细胞生长和肝再生（LR）的影响。使用表达 OPN 和 OPN-siRNA 的重组慢病毒处理 BRL-3A 细胞，而表达 OPN 或 OPN 靶向 shRNA 的腺病毒则用于大鼠原代肝细胞。此外，向 BRL-3A 中添加重组 OPN 和 OPN-Ab。然后进行和实验，以评估 OPN 在肝细胞生长和 LR 中的生物学功能。OPN 过表达促进了 BRL-3A 细胞和原代肝细胞的增殖和活力，而 OPN 沉默则逆转了这些效应。同样，rrOPN 刺激细胞周期进程和活力，但 OPN-Ab 导致细胞周期停滞和活力下降。OPN 过表达诱导 p-STAT3、p-AKT 和 CCND1 的表达，而 OPN siRNA 导致 p-AKT 和 CCND1 的减少。此外，rrOPN 促进了 p-STAT3 和 p-AKT 的表达，而 OPN-Ab 和 PI3K/Akt 抑制剂 LY294002 均抑制了 p-AKT 和 Bcl2 的表达。此外，rrOPN 治疗后，LR 率、血清 IL-6 和 TNF-α、Ki-67 比例以及 STAT3、AKT 和 p65 的磷酸化均增加。OPN 通过 STAT3 和 AKT 信号通路促进肝细胞增殖。
