Suppression of JAK2/STAT3 signaling reduces end-to-end arterial anastomosis induced cell proliferation in common carotid arteries of rats.
Suppression of JAK2/STAT3 signaling reduces end-to-end arterial anastomosis induced cell proliferation in common carotid arteries of rats.
复制标题
抑制 JAK2/STAT3 信号传导可减少大鼠颈总动脉端到端动脉吻合诱导的细胞增殖
DOI：
10.1371/journal.pone.0058730
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hang C
中科院分区：
文献类型：
--
作者：
Zhao J;Zhang M;Li W;Su X;Zhu L;Hang C
据报道，JAK2/STAT3通路在血管内膜损伤后的新生内膜形成中起重要作用。然而，对于该通路在端端动脉吻合（AA）后全层损伤中的作用知之甚少。在此，我们研究了JAK2/STAT3通路在颈总动脉（CCA）吻合诱导的细胞增殖、血管平滑肌细胞（VSMCs）表型改变以及再内皮化中的作用。
成年雄性Wistar大鼠在颈总动脉端端吻合后3、7、14和30天切除颈总动脉。通过蛋白质印迹法和免疫荧光法检测JAK2/STAT3通路的激活，通过定量聚合酶链反应（Q - PCR）和蛋白质印迹法检测增殖细胞核抗原（PCNA）的表达。在AG490（一种JAK2抑制剂）处理下，分别通过蛋白质印迹法、苏木精 - 伊红染色（H&E）、Q - PCR和伊文思蓝染色检测JAK2、STAT3和PCNA的蛋白水平、动脉的形态变化、VSMCs的表型改变以及再内皮化。
磷酸化JAK2（p - JAK2）、磷酸化STAT3（p - STAT3）和PCNA的蛋白水平在动脉吻合后的血管壁中上调，并在第7天达到峰值。AG490下调了第7天组的p - JAK2、p - STAT3和PCNA水平，导致动脉吻合后第7天和第14天血管壁增殖减少。此外，AG490改变了动脉吻合后VSMCs的表型改变，表现为合成期标志物（骨桥蛋白和SMemb）的mRNA水平受到抑制，收缩期标志物（α - 平滑肌肌动蛋白（ASMA）、SM2和SM22α）上调。此外，AG490在动脉吻合后的所有指定时间点（第3、7、14和30天）均不影响再内皮化过程。
我们的研究表明，JAK2/STAT3信号通路在受损血管壁的细胞增殖中起重要作用，并且可能是探索增加动脉吻合后血管通畅性或减少血管狭窄的药物的一个有前景的靶点。
Background JAK2/STAT3 pathway was reported to play an essential role in the neointima formation after vascular intima injury. However, little is known regarding this pathway to the whole layer injury after end-to-end arterial anastomosis (AA). Here, we investigated the role of JAK2/STAT3 pathway in common carotid arterial (CCA) anastomosis-induced cell proliferation, phenotypic change of vascular smooth muscle cells (VSMCs) and re-endothelialization. Methods CCAs of adult male Wistar rats were resected at 3, 7, 14, and 30 days after end-to-end CCA anastomosis. Activation of JAK2/STAT3 pathway was detected by Western blotting and Immunofluorescence, and expression of proliferating cell nuclear antigen (PCNA) was detected by Q-PCR and Western blotting. Under the treatment with AG490 (a JAK2 inhibitor), protein levels of JAK2, STAT3 and PCNA, morphological changes of artery, phenotypic change of VSMCs, and re-endothelialization were measured by Western blotting, H&E, Q-PCR, and Evans blue staining respectively. Results The protein levels of p-JAK2, p-STAT3, and PCNA were up-regulated, peaked on the 7th day in the vessel wall after AA. AG490 down-regulated the levels of p-JAK2, p-STAT3, and PCNA on the 7th-day-group, resulting in reduced vessel wall proliferation on the 7th and 14th day after AA. Besides, AG490 switched the phenotypic change of VSMCs after AA representing inhibited mRNA levels of synthetic phase markers (osteopoitin and SMemb) and up-regulated contractile phase markers (ASMA, SM2 and SM22α). Furthermore, AG490 did not affect the re-endothelialization process on all indicated time points after AA (the 3rd, 7th, 14th, and 30th day). Conclusion Our study indicated that JAK2/STAT3 signaling pathway played an important role on cell proliferation of the injured vessel wall, and probably a promising target for the exploration of drugs increasing the patency or reducing the vascular narrowness after AA.
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影响因子：
2.2
作者：
Maeng, M;Mertz, H;Nielsen, S
通讯作者：
Nielsen, S
DOI：
10.3109/02844318109103422
发表时间：
1981-01-01
影响因子：
--
作者：
LIDMAN, D;DANIEL, RK
通讯作者：
DANIEL, RK
影响因子：
4.1
作者：
Dudley, AC;Thomas, D;Jenkins, A
通讯作者：
Jenkins, A
影响因子：
4.8
作者：
Neeli, I;Liu, ZM;Rao, GN
通讯作者：
Rao, GN
影响因子：
20.1
作者：
LINDNER, V;FINGERLE, J;REIDY, MA
通讯作者：
REIDY, MA