Gap junction protein connexin43 exacerbates lung vascular permeability.
Gap junction protein connexin43 exacerbates lung vascular permeability.
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DOI：
10.1371/journal.pone.0100931
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Birukov KG
中科院分区：
文献类型：
--
作者：
O'Donnell JJ 3rd;Birukova AA;Beyer EC;Birukov KG
血管通透性增加导致肺水肿，损害动脉氧合，从而导致与急性呼吸窘迫综合征和脓毒症相关的发病率和死亡率。虽然细胞间粘附和紧密连接的组成部分是维持内皮屏障的关键，但对间隙连接及其组成蛋白（连接蛋白）的作用的研究有限。由于连接蛋白可以调节其他系统中的炎症信号，我们假设连接蛋白也可以调节肺内皮通透性。在培养的人肺内皮细胞上研究了连接蛋白与炎症刺激的通透性反应之间的关系。凝血酶，脂多糖，或病理性周期性拉伸延长治疗的主要连接蛋白，连接蛋白43（Cx43）的mRNA和蛋白质的水平增加。凝血酶和脂多糖都增加了细胞间的通讯测定转移显微注射荧光黄。虽然凝血酶降低了这些细胞的跨内皮阻力，但用连接蛋白抑制剂甘珀酸预处理可减弱这种反应。此外，凝血酶或脂多糖产生的跨内皮阻力的降低通过siRNA敲低减少Cx43表达而减弱。甘珀酸和Cx43敲低也废除凝血酶诱导的肌球蛋白轻链磷酸化。综上所述，这些数据表明，增加肺血管通透性诱导的炎症条件下，可能会通过增加表达的Cx43和肺内皮细胞之间的细胞间通讯放大。
Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity and mortality associated with Acute Respiratory Distress Syndrome and sepsis. Although components of intercellular adhesive and tight junctions are critical for maintaining the endothelial barrier, there has been limited study of the roles of gap junctions and their component proteins (connexins). Since connexins can modulate inflammatory signaling in other systems, we hypothesized that connexins may also regulate pulmonary endothelial permeability. The relationships between connexins and the permeability response to inflammatory stimuli were studied in cultured human pulmonary endothelial cells. Prolonged treatment with thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels of mRNA and protein for the major connexin, connexin43 (Cx43). Thrombin and lipopolysaccharide both increased intercellular communication assayed by transfer of microinjected Lucifer yellow. Although thrombin decreased transendothelial resistance in these cells, the response was attenuated by pretreatment with the connexin inhibitor carbenoxolone. Additionally, the decreases of transendothelial resistance produced by either thrombin or lipopolysaccharide were attenuated by reducing Cx43 expression by siRNA knockdown. Both carbenoxolone and Cx43 knockdown also abrogated thrombin-induced phosphorylation of myosin light chain. Taken together, these data suggest that increased lung vascular permeability induced by inflammatory conditions may be amplified via increased expression of Cx43 and intercellular communication among pulmonary endothelial cells.
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影响因子：
11.2
作者：
Lim, Philip K.;Bliss, Sarah A.;Rameshwar, Pranela
通讯作者：
Rameshwar, Pranela
影响因子：
3.1
作者：
Fernandez-Cobo, M;Gingalewski, C;De Maio, A
通讯作者：
De Maio, A
DOI：
10.1152/ajplung.00195.2012
发表时间：
2012-10-01
影响因子：
4.9
作者：
Agrawal, Ashish;Zhuo, Hanjing;Liu, Kathleen D.
通讯作者：
Liu, Kathleen D.
连接的共表达37或连接连接与连接蛋白43的共表达有选择地影响细胞间分子转移。
影响因子：
2.4
作者：
Gemel, Joanna;Nelson, Tasha K.;Burt, Janis M.;Beyer, Eric C.
通讯作者：
Beyer, Eric C.
DOI：
10.1152/ajplung.00395.2006
发表时间：
2007-04-01
影响因子：
4.9
作者：
Birukova, Anna A.;Fu, Panfeng;Birukov, Konstantin G.
通讯作者：
Birukov, Konstantin G.