Angiotensin III Induces JAK2/STAT3 Leading to IL-6 Production in Rat Vascular Smooth Muscle Cells
Angiotensin III Induces JAK2/STAT3 Leading to IL-6 Production in Rat Vascular Smooth Muscle Cells
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DOI：
10.3390/ijms20225551
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Clark, Michelle A.
中科院分区：
文献类型：
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作者：
Alanazi, Ahmed Z.;Clark, Michelle A.
Janus 激酶 2/信号转导子和转录激活子 3 (JAK2/STAT3) 途径和白细胞介素 6 (IL-6) 是多效性信号转导系统，负责诱导许多细胞因子和生长因子。目前尚不清楚肾素血管紧张素醛固酮系统 (RAAS) 肽、血管紧张素 (Ang) III 是否诱导血管平滑肌细胞 (VSMC) 中的 JAK2/STAT3 和 IL-6。因此，本研究的目的是调查 Ang III 是否诱导 JAK2/STAT3 通路导致从 Wistar 大鼠分离的培养 VSMC 中产生 IL-6，并确定自发性高血压大鼠 (SHR) VSMC 中是否存在差异。我们通过测量 Ang III 对 STAT3 以及 IL-6 产生的作用来评估 Ang III 对该途径的影响。 Ang III 在刺激 Wistar 和 SHR VSMC 中 STAT3 磷酸化方面的表现与 Ang II 相似。此外，SHR 与 Wistar VSMC 中的 Ang III 效应没有差异。在 Wistar VSMC 中，Ang II 和 Ang III 显着诱导 IL-6 蛋白分泌和 mRNA 表达。然而，这些肽介导的 IL-6 蛋白分泌在 SHR VSMC 中显着增加。 Ang III 诱导 JAK2/STAT3 通路，通过作用于 AT(1)Rs 导致 IL-6 蛋白分泌和 IL-6 mRNA 表达。此外，Ang III 诱导 IL-6 产生的作用在 SHR VSMC 中失调。这些发现表明，Ang III 作用于 AT(1)R，诱导 JAK2/STAT3，导致培养的 VSMC 中 IL-6 增加。这些发现对于确定 Ang III 作为 VSMC 中重要的生理相关肽非常重要。
The Janus kinase-2/ signal transducer and activators of transcription-3 (JAK2/STAT3) pathway and interleukin-6 (IL-6) are pleiotropic signal transduction systems that are responsible for induction of many cytokines and growth factors. It is unknown whether the renin angiotensin aldosterone system (RAAS) peptide, angiotensin (Ang) III induces JAK2/STAT3 and IL-6 in vascular smooth muscle cells (VSMCs). Thus, the purpose of this study was to investigate whether Ang III induces the JAK2/STAT3 pathway leading to IL-6 production in cultured VSMCs isolated from Wistar rats and determine whether differences exist in spontaneously hypertensive rat (SHR) VSMCs. We gauged Ang III's effects on this pathway by measuring its action on STAT3 as well as IL-6 production. Ang III behaved similarly as Ang II in stimulation of STAT3 phosphorylation in Wistar and SHR VSMCs. Moreover, there were no differences in this Ang III effect in SHR versus Wistar VSMCs. In Wistar VSMCs, Ang II and Ang III significantly induced IL-6 protein secretion and mRNA expression. However, IL-6 protein secretions mediated by these peptides were significantly greater in SHR VSMCs. Ang III induced the JAK2/STAT3 pathway, leading to IL-6 protein secretion and IL-6 mRNA expression via actions on AT(1)Rs. Moreover, the actions of Ang III to induce IL-6 production was dysregulated in SHR VSMCs. These findings suggest that Ang III acts on AT(1)Rs to induce JAK2/STAT3, leading to an increase in IL-6 in cultured VSMCs. These findings are important in establishing Ang III as an important physiologically relevant peptide in VSMCs.