下调和上调
肝星状细胞
川地31
癌症研究
细胞生物学
血小板源性生长因子受体
CD44细胞
CXCR4型
趋化因子受体
化学
趋化因子受体
生物
受体
血管生成
内分泌学
内科学
趋化因子
医学
细胞
生长因子
生物化学
基因
作者
Jing Fang,Qiang Ji,Siqi Gao,Zhun Xiao,Wei Liu,Yonghong Hu,Ying Lv,Xianhai Zeng,Yuguang Mu,Hong Cai,Jiamei Chen,Ping Liu
出处
期刊:Heliyon
[Elsevier]
日期:2023-01-01
卷期号:9 (1): e12715-e12715
被引量:2
标识
DOI:10.1016/j.heliyon.2022.e12715
摘要
The activation of HIF-1α/CXCR4 pathway in liver sinusoidal endothelial cells (LSECs) could downregulate CXCR7, leading to the capillarization of LSECs to promote hepatic fibrosis. However, the mechanism between CXCR4 and CXCR7 is still undefined. The aim is to investigate the role of PDGF-BB in the dedifferentiation of LSECs and hepatic stellate cells (HSCs) activation.The activation of HIF-1α/CXCR4 pathway in two kinds of liver fibrosis models were observed. The effects of HIF-1α, CXCR4, PDGF-BB on the dedifferentiation of LSECs were investigated by using the inhibitors of HIF-1α, CXCR4 or PDGFR-β separately or transfecting with a CXCR4 knockdown lentiviral vector. In addition, the relationship between LSECs and HSCs was demonstrated by co-culture of LSECs and HSCs using the transwell chamber.CXCR4 upregulation and CXCR7 downregulation were accompanied by LSECs capillarization and HSCs activation both in CCl4-induced and BDL-induced fibrotic liver. In vitro, downregulation of HIF-1α significantly descreased CXCR4 and CD31 expression, and enhanced the expressions of CXCR7, CD44 and LYVE1. Downregulation of CXCR4 in LSECs significantly downregulated PDGF-BB, PDGFR-β and CD31, and enhanced CXCR7, CD44 and LYVE1 expression, while the expression of HIF-1α did not change significantly. STI571, a PDGF receptor inhibitor, could significantly downregulate PDGFR-β and increase the expression of CXCR7 to inhibit the dedifferentiation of LSECs. In addition, alleviateion the dedifferentiation of LSECs could decrease the expression of PDGFR-β of HSCs, then inhibiting the activation of HSCs.This study revealed that HIF-1α/CXCR4/PDGF-BB/CXCR7 axis promoted the dedifferentiation of LSECs, consequently triggering HSCs activation and liver fibrosis.
科研通智能强力驱动
Strongly Powered by AbleSci AI