JunB mediates basal- and TGFβ1-induced smooth muscle cell contractility.
JunB mediates basal- and TGFβ1-induced smooth muscle cell contractility.
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DOI：
10.1371/journal.pone.0053430
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Adam RM
中科院分区：
文献类型：
--
作者：
Ramachandran A;Gangopadhyay SS;Krishnan R;Ranpura SA;Rajendran K;Ram-Mohan S;Mulone M;Gong EM;Adam RM
平滑肌收缩是由肌动蛋白-肌球蛋白相互作用驱动的动态过程，其由多种调节蛋白控制。我们的研究表明，AP-1转录因子家族的成员控制平滑肌细胞（SMC）的离散行为，如生长，迁移和纤维化。然而，AP-1在调节平滑肌收缩性中的作用尚不完全清楚。在这项研究中，我们发现AP-1家族成员JunB通过改变肌动蛋白聚合和肌球蛋白轻链磷酸化来调节内脏SMC的收缩性。JunB水平在转化生长因子β-1（TGFβ1）下游显著上调，TGF β 1是一种已知的SMC收缩诱导剂。通过凝胶收缩和牵引力显微镜测定，在基础和TGFβ1刺激条件下，RNAi介导的JunB沉默在原代人膀胱SMC（pBSMC）中抑制细胞收缩性。JunB基因敲低并不改变收缩蛋白α-SMA、calponin和SM 22 α的表达。然而，JunB沉默降低了Rho激酶（ROCK）和肌球蛋白轻链（MLC 20）的水平。此外，JunB沉默减弱了MLC 20调节磷酸酶亚基MYPT 1和肌动蛋白切割蛋白cofilin的磷酸化。与这些变化相一致的是，JunB被敲低的细胞显示出对TGFβ1的反应，F：G肌动蛋白比率降低。总之，这些发现表明JunB通过对肌球蛋白和肌动蛋白细胞骨架的影响调节内脏平滑肌细胞收缩性的新功能。
Smooth muscle contraction is a dynamic process driven by acto-myosin interactions that are controlled by multiple regulatory proteins. Our studies have shown that members of the AP-1 transcription factor family control discrete behaviors of smooth muscle cells (SMC) such as growth, migration and fibrosis. However, the role of AP-1 in regulation of smooth muscle contractility is incompletely understood. In this study we show that the AP-1 family member JunB regulates contractility in visceral SMC by altering actin polymerization and myosin light chain phosphorylation. JunB levels are robustly upregulated downstream of transforming growth factor beta-1 (TGFβ1), a known inducer of SMC contractility. RNAi-mediated silencing of JunB in primary human bladder SMC (pBSMC) inhibited cell contractility under both basal and TGFβ1-stimulated conditions, as determined using gel contraction and traction force microscopy assays. JunB knockdown did not alter expression of the contractile proteins α-SMA, calponin or SM22α. However, JunB silencing decreased levels of Rho kinase (ROCK) and myosin light chain (MLC20). Moreover, JunB silencing attenuated phosphorylation of the MLC20 regulatory phosphatase subunit MYPT1 and the actin severing protein cofilin. Consistent with these changes, cells in which JunB was knocked down showed a reduction in the F:G actin ratio in response to TGFβ1. Together these findings demonstrate a novel function for JunB in regulating visceral smooth muscle cell contractility through effects on both myosin and the actin cytoskeleton.
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DOI：
10.1083/jcb.201109045
发表时间：
2012-03-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gervasi M;Bianchi-Smiraglia A;Cummings M;Zheng Q;Wang D;Liu S;Bakin AV
通讯作者：
Bakin AV
DOI：
10.3109/08977194.2011.595714
发表时间：
2011-10
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Biernacka A;Dobaczewski M;Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
5.3
作者：
LAIHO, M;RONNSTRAND, L;MASSAGUE, J
通讯作者：
MASSAGUE, J
影响因子：
6
作者：
Ramachandran, Aruna;Gong, Edward M.;Adam, Rosalyn M.
通讯作者：
Adam, Rosalyn M.
影响因子：
14.9
作者：
Chen, SY;Kulik, M;Lechleider, RJ
通讯作者：
Lechleider, RJ