UCN enhances TGF-beta-mediated mitoinhibition of VSMCs via counteracting TGF-beta-induced cPLA2 expression and activation.
UCN enhances TGF-beta-mediated mitoinhibition of VSMCs via counteracting TGF-beta-induced cPLA2 expression and activation.
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UCN 通过抵消 TGF-β 诱导的 cPLA2 表达和激活来增强 TGF-β 介导的 VSMC 有丝分裂抑制。
DOI：
10.1016/j.biocel.2016.09.028
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
李胜男
中科院分区：
文献类型：
--
作者：
朱超;曹长春;汪晓菲;袁杰;金莱;李胜男
尿皮质素（ucn）和转化生长因子- β (tgf - β)已被证明参与多种心血管疾病，其中许多涉及血管平滑肌细胞（VSMCs）的增殖。胞质磷脂酶A2 （cPLA2）介导的花生四烯酸（AA）释放是VSMCs增殖的重要原因。这项工作是为了研究UCN/ tgf - β对VSMCs增殖的调节，以及cPLA2是否是它们信号通路之间的一个联系。采用比色法和免疫荧光显微镜观察VSMCs的增殖情况。采用细胞流式细胞术观察细胞周期的变化。采用慢病毒载体颗粒过表达cPLA2基因。UCN和tgf - β均能抑制VSMCs的增殖，UCN和tgf - β对VSMCs的增殖有累加作用。tgf - β增加g1期细胞百分比，UCN增加g2期细胞百分比，同时减少s期细胞百分比。此外，tgf - β增加了cPLA2的表达，UCN降低了cPLA2的表达，UCN减弱了tgf - β诱导的cPLA2表达。在原发性VSMCs中，tgf - β诱导cPLA2磷酸化，UCN也减弱了这一作用。与UCN类似，cPLA2抑制剂pyrophenone （PYR）也在增强tgf - β介导的有丝分裂抑制中发挥作用。相反，cPLA2过表达消除了UCN对有丝分裂抑制的作用。UCN预处理可抵消tgf - β介导的cPLA2的表达和激活，从而促进tgf - β介导的VSMCs有丝分裂抑制。
Urocortins (UCNs) and transforming growth factor-beta (TGF-beta) have been demonstrated to participate in various cardiovascular diseases, many of which involve vascular smooth muscle cells (VSMCs) proliferation. Cytosolic phospholipase A2 (cPLA2)-mediated arachidonic acid (AA) release is an important cause of VSMCs proliferation. The work was to investigate the regulation of VSMCs proliferation by UCN/TGF-beta and whether cPLA2 was a link between their signaling pathways. VSMCs proliferation was measured by colorimetric assay and immunofluorescence microscopy. Using cell flow cytometry, the changes in the cell cycle phases were investigated. Lentiviral Vector Particle was performed to overexpress cPLA2 gene. Both UCN and TGF-beta inhibited VSMCs proliferation and an additive effect was observed when the cells were treated with UCN plus TGF-beta. TGF-beta increased the percentage of cells in G1-phase while UCN increased the cell percentage in G2-phase with a concomitant decrease in S-phase. Furthermore, cPLA2 expression was increased by TGF-beta but decreased by UCN and UCN attenuated TGF-beta-induced cPLA2 expression. In primary VSMCs, TGF-beta induced cPLA2 phosphorylation, and this effect was also attenuated by UCN. Similar to UCN, the cPLA2 inhibitor, pyrrophenone (PYR), also played a role in enhancing TGF-beta-mediated mitoinhibition. Inversely, overexpression of cPLA2 eliminated the effect of UCN on the mitoinhibition. The pretreatment with UCN counteracted TGF-beta-mediated cPLA2 expression and activation, thereby contributing to TGF-beta-mediated mitoinhibition of VSMCs.
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影响因子：
13.5
作者：
Han, Chang;Bowen, William C.;Li, Guiying;Demetris, Anthony J.;Michalopoulos, George K.;Wu, Tong
通讯作者：
Wu, Tong
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影响因子：
16.6
作者：
Yoon JH;Sudo K;Kuroda M;Kato M;Lee IK;Han JS;Nakae S;Imamura T;Kim J;Ju JH;Kim DK;Matsuzaki K;Weinstein M;Matsumoto I;Sumida T;Mamura M
通讯作者：
Mamura M
影响因子：
20.1
作者：
Kobayashi, K;Yokote, K;Saito, Y
通讯作者：
Saito, Y
DOI：
10.1074/jbc.272.48.30504
发表时间：
1997-11
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
K. Anderson;A. Roshak;J. Winkler;M. McCord;L. Marshall
通讯作者：
K. Anderson;A. Roshak;J. Winkler;M. McCord;L. Marshall
影响因子：
6
作者：
Emeto, Theophilus I.;Moxon, Joseph V.;Golledge, Jonathan
通讯作者：
Golledge, Jonathan