单位：[1]Experimental Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China医技科室北京市临床医学研究所实验中心首都医科大学附属北京友谊医院[2]National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China首都医科大学附属北京友谊医院[3]Department of Infection Beijing Friendship Hospital, Capital Medical University, Beijing, China临床科室急危重症及感染医学中心感染内科首都医科大学附属北京友谊医院[4]Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China医技科室病理科病理科首都医科大学附属北京友谊医院[5]Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China医技科室检验科检验科首都医科大学附属北京友谊医院
Hepatic fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Migration of the activated HSCs to the site of injury is one of the key characteristics during the wound healing process. We have previously demonstrated that 14 kDa phosphohistidine phosphatase (PHP14) is involved in migration and lamellipodia formation of HSCs. However, the role of PHP14 in liver fibrosis remains unknown. In this study, we first assessed PHP14 expression and distribution in liver fibrotic tissues using western blot, immunohistochemistry, and double immunofluorescence staining. Next, we investigated the role of PHP14 in liver fibrosis and, more specifically, the migration of HSCs by Transwell assay and 3D collagen matrices assay. Finally, we explored the possible molecular mechanisms of the effects of PHP14 on these processes. Our results show that the PHP14 expression is upregulated in fibrotic liver and mainly in HSCs. Importantly, TGF-beta 1 can induce PHP14 expression in HSCs accompanied with the activation of HSCs. Consistent with the previous study, PHP14 promotes HSCs migration, especially, promotes 3D floating collagen matrices contraction but inhibits stressed-released matrices contraction. Mechanistically, the PI3K gamma/AKT/Rac1 pathway is involved in migration regulated by PHP14. Moreover, PHP14 specifically mediates the TGF-beta 1 signaling to PI3K gamma/AKT pathway and regulates HSC migration, and thus participates in liver fibrosis. Our study identified the role of PHP14 in liver fibrosis, particularly HSC migration, and suggested a novel mediator of transducting TGF-beta 1 signaling to PI3K gamma/AKT/Rac1 pathway.
基金：
Beijing Talents Fund [2016000021469G227]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81071973]; Wang Bao-En Liver Fibrosis Foundation [20100013]; Beijing Friendship Hospital [yyqdkt201516]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区遗传学2 区医学：研究与实验
最新[2025]版：
大类|3 区医学
小类|3 区遗传学3 区医学：研究与实验
JCR分区：
出版当年[2016]版：
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1GENETICS & HEREDITY
最新[2023]版：
Q1GENETICS & HEREDITYQ1MEDICINE, RESEARCH & EXPERIMENTAL
第一作者单位：[1]Experimental Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China[2]National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China
通讯作者：
通讯机构：[1]Experimental Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China[2]National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Xu Anjian,Li Yanmeng,Zhao Wenshan,et al.PHP14 regulates hepatic stellate cells migration in liver fibrosis via mediating TGF-beta 1 signaling to PI3K gamma/AKT/Rac1 pathway[J].JOURNAL of MOLECULAR MEDICINE-JMM.2018,96(2):119-133.doi:10.1007/s00109-017-1605-6.
APA：
Xu, Anjian,Li, Yanmeng,Zhao, Wenshan,Hou, Fei,Li, Xiaojin...&Huang, Jian.(2018).PHP14 regulates hepatic stellate cells migration in liver fibrosis via mediating TGF-beta 1 signaling to PI3K gamma/AKT/Rac1 pathway.JOURNAL of MOLECULAR MEDICINE-JMM,96,(2)
MLA：
Xu, Anjian,et al."PHP14 regulates hepatic stellate cells migration in liver fibrosis via mediating TGF-beta 1 signaling to PI3K gamma/AKT/Rac1 pathway".JOURNAL of MOLECULAR MEDICINE-JMM 96..2(2018):119-133
