Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver.
Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver.
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沉默 IQGAP1 通过阻止骨髓间充质基质细胞募集至纤维化肝脏来减轻肝纤维化
DOI：
10.1016/j.omtn.2021.12.020
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发表时间：
2022-03-08
期刊：
影响因子：
--
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Ma Y;Chang N;Liu Y;Liu F;Dong C;Hou L;Qi C;Yang L;Li L
含IQ基序鸟苷三磷酸酶（GTPase）激活蛋白1 （IQGAP1）是一种参与细胞迁移的胞质支架蛋白。我们之前的研究表明，鞘氨醇1-磷酸（S1P）触发骨髓间充质间质细胞（BMSCs）向受损肝脏转移，从而促进肝纤维化。然而，IQGAP1在s1p诱导的BMSC迁移和肝纤维化中的作用尚不清楚。用EGFP标记的BM细胞嵌合小鼠构建蛋氨酸-胆碱缺乏和高脂肪（MCDHF）饮食诱导的小鼠肝纤维化。利用IQGAP1小干扰RNA （siRNA）在体内沉默IQGAP1。在mcdhf饮食诱导的小鼠纤维化肝中，IQGAP1的表达显著升高。在人和小鼠纤维化肝中，IQGAP1与纤维化标志物的表达呈正相关。体外，抑制IQGAP1表达可阻断s1p诱导的骨髓间充质干细胞运动和细胞骨架重塑。S1P通过S1P受体3 （S1PR3）和Cdc42/Rac1促进IQGAP1聚集到质膜上。此外，IQGAP1结合Cdc42/Rac1，协同调节s1p诱导的Cdc42/Rac1的激活和介导BMSC迁移。在体内，沉默IQGAP1可减少BMSCs向受损肝脏的募集，有效缓解MCDHF饮食诱导的肝纤维化。总之，沉默IQGAP1通过阻断BMSC迁移来缓解肝纤维化，为肝纤维化提供了有效的治疗策略。IQGAP1在小鼠肝纤维化过程中升高，与小鼠和人类纤维化肝的纤维化标志正相关。IQGAP1通过鞘氨醇1-磷酸受体3和Cdc42/Rac1介导骨髓间充质基质细胞（BMSC）迁移的质膜重分布。沉默IQGAP1可通过阻断BMSC向损伤肝脏的募集来减轻肝纤维化。
IQ motif-containing guanosine triphosphatase (GTPase)-activating protein 1 (IQGAP1) is a cytosolic scaffolding protein involved in cell migration. Our previous studies suggest sphingosine 1-phosphate (S1P) triggers bone marrow (BM) mesenchymal stromal cells (BMSCs) to damaged liver, thereby promoting liver fibrosis. However, the role of IQGAP1 in S1P-induced BMSC migration and liver fibrogenesis remains unclear. Chimeric mice of BM cell labeled by EGFP were used to build methionine-choline-deficient and high-fat (MCDHF)-diet-induced mouse liver fibrosis. IQGAP1 small interfering RNA (siRNA) was utilized to silence IQGAP1 in vivo. IQGAP1 expression is significantly elevated in MCDHF-diet-induced mouse fibrotic livers. Positive correlations are presented between IQGAP1 and fibrosis hallmarks expressions in human and mouse fibrotic livers. In vitro, depressing IQGAP1 expression blocks S1P-induced motility and cytoskeleton remodeling of BMSCs. S1P facilitates IQGAP1 aggregating to plasma membrane via S1P receptor 3 (S1PR3) and Cdc42/Rac1. In addition, IQGAP1 binds to Cdc42/Rac1, regulating S1P-induced activation of Cdc42/Rac1 and mediating BMSC migration in concert. In vivo, silencing IQGAP1 reduces the recruitment of BMSCs to impaired liver and effectively alleviates liver fibrosis induced by MCDHF diet. Together, silencing IQGAP1 relieves liver fibrosis by blocking BMSC migration, providing an effective therapeutic strategy for liver fibrosis. IQGAP1 is increased during murine liver fibrogenesis and positively related to fibrosis hallmarks in mouse and human fibrotic livers. IQGAP1 mediates bone marrow mesenchymal stromal cell (BMSC) migration by plasma membrane redistribution dependent on sphingosine 1-phosphate receptor 3 and Cdc42/Rac1. Silencing IQGAP1 alleviates hepatic fibrosis via blocking BMSC recruitment to injured liver.
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影响因子：
25.7
作者：
Li, Changyong;Kong, Yaxian;Li, Liying
通讯作者：
Li, Liying
影响因子：
11
作者：
Liu YW;Chiu YT;Fu SL;Huang YT
通讯作者：
Huang YT
DOI：
10.1152/ajplung.00530.2007
发表时间：
2008-10-01
影响因子：
4.9
作者：
Bogatkevich, Galina S.;Ludwicka-Bradley, Anna;Silver, Richard M.
通讯作者：
Silver, Richard M.
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影响因子：
8.8
作者：
Mo CF;Li J;Yang SX;Guo HJ;Liu Y;Luo XY;Wang YT;Li MH;Li JY;Zou Q
通讯作者：
Zou Q
IQGAP1 通过 Wnt/β-catenin 信号传导促进胰腺癌进展和上皮间质转化 (EMT)
影响因子：
4.6
作者：
Hu, Wei;Wang, Zhongxia;Jiang, Chunping
通讯作者：
Jiang, Chunping