鸢尾素抑制JAK/STAT3通路促进炎症状态下的血管生成

doi:10.13418/j.issn.1001-165x.2021.06.012

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中国临床解剖学杂志 ›› 2021, Vol. 39 ›› Issue (6) : 680-685. DOI: 10.13418/j.issn.1001-165x.2021.06.012

实验研究

鸢尾素抑制JAK/STAT3通路促进炎症状态下的血管生成

胡思涵^{1, 2}，　薛源^{1, 2}，　金叶盛²，　张元澍²，　施勤¹，　芮永军²

作者信息 +

Irisin promotes angiogenesis in inflammatory state by inhibiting the JAK/STAT3 pathway

Hu Sihan^1,2, Xue Yuan^1,2, Jin Yesheng², Zhang Yuanshu², Shi Qin¹, Rui Yongjun²

Author information +

文章历史 +

摘要

目的　研究急性炎症状态下鸢尾素对人脐静脉内皮细胞（human umbilical vein endothelial cell，HUVEC）血管生成的影响及其机制。方法　通过CCK-8检测不同浓度（0.1、1.0、5.0、10.0、20.0 ng/mL）的鸢尾素对HUVEC增殖的影响；用脂多糖诱导HUVEC急性炎症状态，通过划痕和成管实验，研究鸢尾素对细胞迁移及管样形成的影响，通过RT-PCR研究相关细胞因子IL-1β、IL-6、TNF-α、PDGF-BB的基因表达；Western blot检测JAK／STAT3信号通路中关键蛋白Erk1／2、Jak、Stat3的表达。结果　各浓度的重组鸢尾素均不影响HUVEC的增殖；在急性炎症状态下，鸢尾素可以促进HUVEC细胞迁移和管样形成，并且抑制HUVEC炎症因子IL-1β、IL-6、TNF-α基因的表达，增加组织修复相关因子PDGF-BB的基因表达；鸢尾素抑制LPS诱导的JAK／STAT3通路激活。结论　鸢尾素可以抑制JAK／STAT3信号通路，缓解LPS诱导的HUVEC急性炎症状态，促进血管新生。

Abstract

Objective　To investigate the effect of irisin on angiogenesis in human umbilical vein endothelial cell (HUVEC) under acute inflammatory state and its regulatory mechanism.　Methods　 (1)The effects of different concentrations (0.1, 1.0, 5.0, 10.0, 20.0 ng/ml) of irisin on HUVEC proliferation were detected by CCK-8; (2) Acute inflammatory state of HUVEC was induced by LPS. The effect of irisin on cell migration and tubular formation was studied by scratch and tube forming experiments. The gene expression of related cytokines IL-1β, IL-6, TNF-α and PDGF-BB was studied by RT-PCR; (3) The expressions of proteins Erk1/2, Jak and Stat3 in the JAK/STAT3 signaling pathway were detected by Western Blot.　Results　 (1) The change of concentrations of recombinant irisin did not affect the proliferation of HUVEC; (2) Irisin promoted cell migration and tubular formation of HUVEC in the state of acute inflammation, and inhibited the expression of inflammatory factors IL-1β, IL-6 and TNF-α in HUVEC in the state of acute inflammation, and increased the gene expression of tissue repair factor PDGF-BB; (3) Irisin inhibited LPS-induced activation of the JAK/STAT3 pathway.　Conclusions　Irisin suppresses JAK/STAT3 signaling pathway, relieves acute inflammatory state of HUVEC induced by LPS, and promotes angiogenesis.

导出引用

胡思涵, 薛源, 金叶盛, 张元澍, 施勤, 芮永军. 鸢尾素抑制JAK/STAT3通路促进炎症状态下的血管生成[J]. 中国临床解剖学杂志. 2021, 39(6): 680-685 https://doi.org/10.13418/j.issn.1001-165x.2021.06.012

Hu Sihan, Xue Yuan, Jin Yesheng, Zhang Yuanshu, Shi Qin, Rui Yongjun. Irisin promotes angiogenesis in inflammatory state by inhibiting the JAK/STAT3 pathway[J]. Chinese Journal of Clinical Anatomy. 2021, 39(6): 680-685 https://doi.org/10.13418/j.issn.1001-165x.2021.06.012

中图分类号： R339.37

参考文献

[1] Khojasteh A, Kheiri L, Motamedian SR, et al. Guided bone regeneration for the reconstruction of alveolar bone defects[J]. Ann Maxillofac Surg, 2017, 7(2): 263-277. DOI: 10.4103/ams.ams_76_17.
[2] 马启明, 庄跃宏. 皮瓣移植术后血管痉挛机制与解痉挛药物研究进展[J]. 中国临床解剖学杂志, 2020, 38(2): 231-234. DOI: 10.13418/j.issn.1001-165x.2020.02.027.
[3] van den Heuvel MG, Buurman WA, Bast A, et al. Review: Ischaemia-reperfusion injury in flap surgery[J]. J Plast Reconstr Aesthet Surg, 2009, 62(6): 721-726. DOI: 10.1016/j.bjps.2009.01.060.
[4] Cui H, Feng YY, Shu CL, et al. Dietary nitrate protects against skin flap ischemia-reperfusion injury in rats via modulation of antioxidative action and reduction of inflammatory responses[J]. Front Pharmacol, 2019, 10(1605): 1-10. DOI: 10.3389/fphar.2019.01605.
[5] He JB, Fang MJ, Ma XY, et al. Angiogenic and anti-inflammatory properties of azadirachtin A improve random skin flap survival in rats[J]. Exp Biol Med (Maywood), 2020, 245(18): 1672-1682. DOI: 10.1177/1535370220951896.
[6] Li YY, Zhang GY, He JP, et al. Ufm1 inhibits LPS-induced endothelial cell inflammatory responses through the NF-kappaB signaling pathway[J]. Int J Mol Med, 2017, 39(5): 1119-1126. DOI: 10.3892/ijmm.2017.2947.
[7] Linghu KG, Wu GP, Fu LY, et al. 1,8-Cineole ameliorates LPS-induced vascular endothelium dysfunction in mice via PPAR-gamma dependent regulation of NF-kappaB[J]. Front Pharmacol, 2019, 10: 178. DOI: 10.3389/fphar.2019.00178.
[8] Mazur-Bialy AI, Bilski J, Pochec E, et al. New insight into the direct anti-inflammatory activity of a myokine irisin against proinflammatory activation of adipocytes. Implication for exercise in obesity[J]. J Physiol Phamacol, 2017, 68（2）: 243-251.
[9] Boström P, Wu J, Jedrychowski MP, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis[J]. Nature, 2012, 481(7382): 463-468. DOI: 10.1038/nature10777.
[10]Liu TY, Shi CX, Gao R, et al. Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes[J]. Clin Sci (Lond), 2015, 129(10): 839-850. DOI: 10.1042/cs20150009.
[11]Xiong XQ, Geng Z, Zhou B, et al. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity[J]. Metabolism, 2018, 83: 31-41. DOI: 10.1016/j.metabol.2018.01.013.
[12]Zhao G, Zhang X, Xu P, et al. The protective effect of Irisin against ischemia-reperfusion injury after perforator flap grafting in rats[J]. Injury, 2018, 49(12): 2147-2153. DOI: 10.1016/j.injury.2018.09.054.
[13]Jedrychowski MP, Wrann CD, Paulo JA, et al. Detection and quantitation of circulating human Iirisin by tandem mass spectrometry[J]. Cell Metab, 2015, 22(4): 734-740. DOI: 10.1016/j.cmet. 2015. 08. 001.
[14]Zhang YT, Hao ZC, Wang PF, et al. Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1alpha-mediated promotion of angiogenesis in a rat model of stabilized fracture[J]. Cell Prolif, 2019, 52(2): e12570. DOI: 10.1111/cpr.12570.
[15]Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development[J]. Cell, 2019, 176(6): 1248-1264. DOI: 10.1016/j.cell.2019.01.021.
[16]Jetten N, Verbruggen S, Gijbels MJ, et al. Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo[J]. Angiogenesis, 2014, 17(1): 109-118. DOI: 10.1007/s10456-013-9381-6.
[17]DiPietro LA. Angiogenesis and wound repair: when enough is enough[J]. J Leukoc Biol, 2016, 100(5): 979-984. DOI: 10.1189/jlb.4MR0316-102R.
[18]Eming SA, Wynn TA, Martin P. Inflammation and metabolism in tissue repair and regeneration[J]. Science, 2017, 356(6342): 1026-1030. DOI: 10.1126/science.aam7928.
[19]Vannella KM, Wynn TA. Mechanisms of organ injury and repair by macrophages[J]. Annu Rev Physiol, 2017, 79: 593-617. DOI: 10.1146/annurev-physiol-022516-034356.
[20]Hu YS, Han X, Liu XH. STAT3: a potential drug target for tumor and inflammation[J]. Curr Top Med Chem, 2019, 19(15): 1305-1317. DOI: 10.2174/1568026619666190620145052.
[21]Zhao J, Du PZ, Cui P, et al. LncRNA PVT1 promotes angiogenesis via activating the STAT3/VEGFA axis in gastric cancer[J]. Oncogene, 2018, 37(30): 4094-4109. DOI: 10.1038/s41388-018-0250-z.