Protective effects of SOCS3 overexpression in high glucose‑induced lung epithelial cell injury through the JAK2/STAT3 pathway.
Protective effects of SOCS3 overexpression in high glucose‑induced lung epithelial cell injury through the JAK2/STAT3 pathway.
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DOI：
10.3892/mmr.2017.6941
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发表时间：
2017-09
影响因子：
3.4
通讯作者：
Leng Y
中科院分区：
文献类型：
--
作者：
Duan WN;Xia ZY;Liu M;Sun Q;Lei SQ;Wu XJ;Meng QT;Leng Y
以往的研究表明Janus激酶（JAK）/信号转导和转录激活因子（STAT）通路参与了高血糖引起的肺损伤。本研究旨在探讨细胞因子信号转导抑制因子3（SOCS 3）在高糖诱导人肺上皮细胞A549 JAK 2/STAT 3活化中的作用。使用细胞计数试剂盒-8和乳酸脱氢酶测定法评价细胞活力。采用ELISA法检测A549细胞中白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平，评价HG诱导的A549细胞炎症损伤。使用蛋白质印迹分析测定SOCS 3、JAK 2、STAT 3、磷酸化（p）-JAK 2和p-STAT 3的蛋白质表达水平。HG刺激A549细胞后，细胞活力显著下降，而IL-6和TNF-α水平显著升高。另外，HG处理的细胞中SOCS 3、p-JAK 2和p-STAT 3的蛋白水平显著增加。用JAK 2/STAT 3抑制剂tyrphostin AG 490或SOCS 3过表达处理似乎可以防止HG诱导的蛋白质表达改变。此外，细胞活力增强，而促炎细胞因子的水平受到抑制。这些发现表明SOCS 3/JAK 2/STAT 3信号通路参与了HG诱导的肺细胞反应。因此，可以假设通过SOCS 3过表达抑制JAK 2/STAT 3通路可以预防高血糖诱导的肺损伤，并且可能具有治疗糖尿病肺损伤患者的治疗潜力。
Previous studies have suggested that the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway is involved in hyperglycemia-induced lung injury. The present study aimed to investigate the roles of suppressor of cytokine signaling3 (SOCS3) in the regulation of JAK2/STAT3 activation following high glucose (HG) treatment in A549 human pulmonary epithelial cells. Cell viability was evaluated using Cell Counting Kit-8 and lactate dehydrogenase assays. HG-induced inflammatory injury in A549 cells was assessed through the evaluation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels using ELISA. The protein expression levels of SOCS3, JAK2, STAT3, phosphorylated (p)-JAK2 and p-STAT3 were determined using western blot analysis. Cellular viability was significantly decreased, whereas IL-6 and TNF-α levels were significantly increased, following HG stimulation of A549 cells. In addition, the protein levels of SOCS3, p-JAK2 and p-STAT3 were significantly increased in HG-treated cells. Treatment with the JAK2/STAT3 inhibitor tyrphostin AG490, or SOCS3 overexpression, appeared to prevent the HG-induced alterations in protein expression. Furthermore, cellular viability was enhanced, whereas the levels of proinflammatory cytokines were suppressed. These finding suggested the involvement of the SOCS3/JAK2/STAT3 signaling pathway in HG-induced responses in lung cells. Therefore, it may be hypothesized that the inhibition of the JAK2/STAT3 pathway through SOCS3 overexpression may prevent hyperglycemia-induced lung injury, and may have therapeutic potential for the treatment of patients with diabetic lung injury.
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DOI：
10.4161/jkst.24053
发表时间：
2013-07-01
期刊：
JAK-STAT
影响因子：
--
作者：
Inagaki-Ohara K;Kondo T;Ito M;Yoshimura A
通讯作者：
Yoshimura A
影响因子：
3.2
作者：
Liu, Qingjuan;Xing, Lingling;Duan, Huijun
通讯作者：
Duan, Huijun
影响因子：
4.4
作者：
Gómez-Guerrero, C;López-Franco, O;Egido, J
通讯作者：
Egido, J
影响因子：
14.2
作者：
Nakashima, Taku;Yokoyama, Akihito;Kohno, Nobuoki
通讯作者：
Kohno, Nobuoki
影响因子：
4.4
作者：
Gao, Hongwei;Hoesel, L. Marco;Ward, Peter A.
通讯作者：
Ward, Peter A.