Liao Lin, Zheng Binwu, Yi Bin, Liu Chang, Chen Lin, Zeng Ziyang, Gao Jing
Department of Anesthesia, People's Hospital of Qijiang District, Chongqing 401420, China.
Department of Anesthesia, People's Hospital of Rongchang County, Chongqing 402460, China.
Exp Cell Res. 2017 Oct 1;359(1):266-274. doi: 10.1016/j.yexcr.2017.07.020. Epub 2017 Jul 17.
We have established that annexin A2 (ANXA2) is an important factor in the experimental hepatopulmonary syndrome (HPS) serum-induced proliferation of pulmonary arterial smooth muscle cells (PASMCs). However, the detailed mechanism remains unclear. ANXA2 translocated to the caveolin-enriched microdomains (caveolae) in PASMCs upon HPS serum stimulation. The disruption of caveolae by Methyl-β-cyclodextrin (MβCD) alleviated the caveolae recruitment of ANXA2 and the ANXA2-mediated activation of ERK1/2 and NF-κB, so that ANXA2-modulated PASMC proliferation was suppressed. The over-expression of Cav-1 resulted in the relocation of ANXA2 from caveolae and negatively regulated ERK1/2 and NF-κB activation, which inhibited the ANXA2-modulated PASMC proliferative behavior. These data indicate that caveolae function as a signaling platform for ANXA2-induced proliferative behavior and Cav-1 participates upstream of ANXA2 in the activation of ERK1/2 and NF-κB.
我们已经确定，膜联蛋白A2（ANXA2）是实验性肝肺综合征（HPS）血清诱导肺动脉平滑肌细胞（PASMCs）增殖的一个重要因素。然而，具体机制仍不清楚。在HPS血清刺激下，ANXA2转位至PASMCs中富含小窝蛋白的微结构域（小窝）。甲基-β-环糊精（MβCD）破坏小窝减轻了ANXA2的小窝募集以及ANXA2介导的细胞外信号调节激酶1/2（ERK1/2）和核因子κB（NF-κB）的激活，从而抑制了ANXA2调节的PASMCs增殖。小窝蛋白-1（Cav-1）的过表达导致ANXA2从小窝重新定位，并负向调节ERK1/2和NF-κB的激活，进而抑制ANXA2调节的PASMCs增殖行为。这些数据表明，小窝作为ANXA2诱导增殖行为的信号平台，且Cav-1在ERK1/2和NF-κB激活过程中参与ANXA2上游的作用。
