BMP9 Induces Mature Differentiation of Liver Progenitor Cells through ALK1/2 Signaling Pathway
LIU Daijiang1, WAN Xiaoqiang1, CHEN Jia1, LI Wen1, WANG Yinguang2*
This study aimed to investigate the effect of BMP9 (bone morphogenetic protein 9) on induction of mature differentiation of liver progenitor cells through ALK1/ALK2 signaling pathway. HP14-19 (hepatic progenitor cell 14-19) was infected with adenovirus-siALK1 and siALK2. The expressions of ALK1 and ALK2 are detected by Real-time PCR and Western blot. Relative acitvity ALB-Gluc was detected by luciferase reporter assay and the mRNA expression of liver related genes AFP, ALB, CK18 and ApoB were detected by Real-time PCR. PAS staining and ICG uptake assay were used to detect the metabolism and glycogen synthesis of hepatocytes. The results showed that Ad-siALK1 and Ad-siALK2 infection could specifically inhibit the expression of ALK1 and ALK2 in HP14-19 cells, and BMP9 could induce the mature differentiation and hepatic function of HP14-19 cells. With BMP9 induction, cell morphology showed polygonal paving stone shape, ALB-Gluc activity was significantly increased, and the expression of liver stem cells marker AFP was down-regulated, while the expressions of hepatic related markers ALB, CK18 and ApoB in mature hepatocytes were significantly up-regulated, and the number of ICG and PAS staining positive cells increased. In AdsiALK1 and Ad-siALK2 treated groups, the expressions of hepatic mature markers, detoxification metabolism and glycogen synthesis decreased. In conclusion, BMP9 might induce mature differentiation of liver progenitor cells through ALK1/ALK2 signaling.
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