Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
Int J Mol Sci. 2019 Nov 7;20(22):5551. doi: 10.3390/ijms20225551.
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 ATRs. Moreover, the actions of Ang III to induce IL-6 production was dysregulated in SHR VSMCs. These findings suggest that Ang III acts on ATRs 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.
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 是否会在血管平滑肌细胞（VSMCs）中诱导 JAK2/STAT3 和 IL-6。因此，本研究的目的是研究 Ang III 是否会诱导 JAK2/STAT3 途径导致从 Wistar 大鼠分离的培养的 VSMCs 中产生 IL-6，并确定自发性高血压大鼠（SHR）VSMCs 是否存在差异。我们通过测量 STAT3 的作用以及 IL-6 的产生来衡量 Ang III 对该途径的影响。Ang III 在 Wistar 和 SHR VSMCs 中刺激 STAT3 磷酸化的作用与 Ang II 相似。此外，在 SHR 与 Wistar VSMCs 之间，这种 Ang III 作用没有差异。在 Wistar VSMCs 中，Ang II 和 Ang III 显著诱导 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 VSMCs 中显著增加。Ang III 通过作用于 ATRs 诱导 JAK2/STAT3 途径，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 VSMCs 中失调。这些发现表明，Ang III 通过作用于 ATRs 诱导 JAK2/STAT3，导致培养的 VSMCs 中 IL-6 增加。这些发现对于将 Ang III 确立为 VSMCs 中重要的生理相关肽具有重要意义。
