哮喘中的磷酸肌醇3激酶：新作用与治疗方法
Phosphoinositide 3-Kinase in Asthma: Novel Roles and Therapeutic Approaches.
作者信息
Yoo Edwin J, Ojiaku Christie A, Sunder Krishna, Panettieri Reynold A
机构信息
1 Rutgers Institute for Translational Medicine and Science, Rutgers, the State University of New Jersey, New Brunswick, New Jersey; and.
2 Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
出版信息
Am J Respir Cell Mol Biol. 2017 Jun;56(6):700-707. doi: 10.1165/rcmb.2016-0308TR.
Abstract
Asthma manifests as airway hyperresponsiveness and inflammation, including coughing, wheezing, and shortness of breath. Immune cells and airway structural cells orchestrate asthma pathophysiology, leading to mucus secretion, airway narrowing, and obstruction. Phosphoinositide 3-kinase, a lipid kinase, plays a crucial role in many of the cellular and molecular mechanisms driving asthma pathophysiology and represents an attractive therapeutic target. Here, we summarize the diverse roles of phosphoinositide 3-kinase in the pathogenesis of asthma and discuss novel therapeutic approaches to treatment.
摘要
哮喘表现为气道高反应性和炎症，包括咳嗽、喘息和呼吸急促。免疫细胞和气道结构细胞共同参与哮喘的病理生理过程，导致黏液分泌、气道狭窄和阻塞。磷脂酰肌醇3-激酶作为一种脂质激酶，在驱动哮喘病理生理的许多细胞和分子机制中起着关键作用，是一个有吸引力的治疗靶点。在此，我们总结了磷脂酰肌醇3-激酶在哮喘发病机制中的多种作用，并讨论了新的治疗方法。
相似文献
1
Phosphoinositide 3-Kinase in Asthma: Novel Roles and Therapeutic Approaches.哮喘中的磷酸肌醇3激酶：新作用与治疗方法
Am J Respir Cell Mol Biol. 2017 Jun;56(6):700-707. doi: 10.1165/rcmb.2016-0308TR.
2
Targeting phosphoinositide 3-kinase δ for allergic asthma.针对磷酸肌醇 3-激酶 δ 的变应性哮喘治疗。
Biochem Soc Trans. 2012 Feb;40(1):240-5. doi: 10.1042/BST20110665.
3
PI 3-kinase inhibition: a therapeutic target for respiratory disease.磷脂酰肌醇-3激酶抑制：呼吸系统疾病的治疗靶点。
Biochem Soc Trans. 2004 Apr;32(Pt 2):378-82. doi: 10.1042/bst0320378.
4
Inhibition of phosphoinositide 3-kinase delta attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model.抑制磷酸肌醇3激酶δ可减轻小鼠哮喘模型中的过敏性气道炎症和高反应性。
FASEB J. 2006 Mar;20(3):455-65. doi: 10.1096/fj.05-5045com.
5
An anti-inflammatory role for a phosphoinositide 3-kinase inhibitor LY294002 in a mouse asthma model.磷酸肌醇3激酶抑制剂LY294002在小鼠哮喘模型中的抗炎作用
Int Immunopharmacol. 2005 Mar;5(3):495-502. doi: 10.1016/j.intimp.2004.10.015.
6
The pathophysiological roles of PI3Ks and therapeutic potential of selective inhibitors in allergic inflammation.PI3Ks 在过敏炎症中的病理生理作用及选择性抑制剂的治疗潜力。
Int Arch Allergy Immunol. 2010;152 Suppl 1:90-5. doi: 10.1159/000312132. Epub 2010 Jun 4.
7
Targeting phosphoinositide 3-kinase δ for the treatment of respiratory diseases.针对磷酸肌醇 3-激酶 δ 治疗呼吸疾病。
Ann N Y Acad Sci. 2013 Mar;1280:35-9. doi: 10.1111/nyas.12039.
8
The potential use of tyrosine kinase inhibitors in severe asthma.酪氨酸激酶抑制剂在重症哮喘中的潜在应用。
Curr Opin Allergy Clin Immunol. 2012 Feb;12(1):68-75. doi: 10.1097/ACI.0b013e32834ecb4f.
9
Blockade of inflammation and airway hyperresponsiveness in immune-sensitized mice by dominant-negative phosphoinositide 3-kinase-TAT.显性负性磷酸肌醇3激酶-TAT对免疫致敏小鼠炎症和气道高反应性的阻断作用
J Exp Med. 2003 Nov 17;198(10):1573-82. doi: 10.1084/jem.20030298.
10
The role of PTEN in allergic inflammation.PTEN在过敏性炎症中的作用。
Arch Immunol Ther Exp (Warsz). 2004 Jul-Aug;52(4):250-4.
引用本文的文献
1
Childhood Asthma Biomarkers Derived from Plasma and Saliva Exosomal miRNAs.源自血浆和唾液外泌体微小RNA的儿童哮喘生物标志物
Int J Mol Sci. 2025 Jul 22;26(15):7043. doi: 10.3390/ijms26157043.
2
The Mechanisms and Therapeutic Implications of PI3K Signaling in Airway Inflammation and Remodeling in Asthma.PI3K信号通路在哮喘气道炎症和重塑中的机制及治疗意义
Biologics. 2025 Mar 7;19:73-86. doi: 10.2147/BTT.S497622. eCollection 2025.
3
Oxidative stress in asthma pathogenesis: mechanistic insights and implications for airway smooth muscle dysfunction.哮喘发病机制中的氧化应激：作用机制及对气道平滑肌功能障碍的影响
Cell Tissue Res. 2025 Apr;400(1):17-34. doi: 10.1007/s00441-025-03953-7. Epub 2025 Feb 7.
4
A PI3Kδ-Foxo1-FasL signaling amplification loop rewires CD4 T helper cell signaling, differentiation and epigenetic remodeling.PI3Kδ-Foxo1-FasL信号放大环重塑CD4辅助性T细胞信号传导、分化和表观遗传重塑。
bioRxiv. 2024 Nov 2:2024.10.28.620691. doi: 10.1101/2024.10.28.620691.
5
Network pharmacology and experimental verification unraveled the mechanism of Bailing Capsule against asthma.网络药理学与实验验证揭示了百灵胶囊治疗哮喘的作用机制。
Medicine (Baltimore). 2024 Nov 1;103(44):e40391. doi: 10.1097/MD.0000000000040391.
6
PI3Kγδ inhibition suppresses key disease features in a rat model of asthma.PI3Kγδ抑制可抑制哮喘大鼠模型的关键疾病特征。
Respir Res. 2024 Apr 23;25(1):175. doi: 10.1186/s12931-024-02814-1.
7
The Expression of Semaphorin3E in Vagal Ganglion and Lung Tissue Is Related to Airway Hyperresponsiveness in Murine Asthma Model.Semaphorin3E 在迷走神经节和肺组织中的表达与哮喘模型小鼠的气道高反应性有关。
J Immunol Res. 2023 Dec 11;2023:6459234. doi: 10.1155/2023/6459234. eCollection 2023.
8
PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model.PP121，一种酪氨酸和磷酸肌醇激酶的双重抑制剂，可缓解哮喘小鼠模型中的气道高反应性、黏液高分泌和炎症。
Mol Med. 2023 Nov 7;29(1):154. doi: 10.1186/s10020-023-00748-w.
9
Unraveling the link between PTBP1 and severe asthma through machine learning and association rule mining method.通过机器学习和关联规则挖掘方法揭示 PTBP1 与严重哮喘之间的联系。
Sci Rep. 2023 Sep 16;13(1):15399. doi: 10.1038/s41598-023-42581-5.
10
Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: a multicentre prospective study.婴儿严重毛细支气管炎与儿童哮喘风险的鼻腔气道 microRNA 谱分析：一项多中心前瞻性研究。
Eur Respir J. 2023 Aug 3;62(2). doi: 10.1183/13993003.00502-2023. Print 2023 Aug.
本文引用的文献
1
Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease.激酶作为哮喘和慢性阻塞性肺疾病的新型治疗靶点。
Pharmacol Rev. 2016 Jul;68(3):788-815. doi: 10.1124/pr.116.012518.
2
Inhibition of PI3K promotes dilation of human small airways in a rho kinase-dependent manner.抑制PI3K以一种依赖于Rho激酶的方式促进人小气道扩张。
Br J Pharmacol. 2016 Sep;173(18):2726-38. doi: 10.1111/bph.13542. Epub 2016 Aug 3.
3
TNFα promotes CAR-dependent migration of leukocytes across epithelial monolayers.TNFα 促进 CAR 依赖性白细胞穿过上皮细胞单层的迁移。
Sci Rep. 2016 May 19;6:26321. doi: 10.1038/srep26321.
4
MiR-221 promotes IgE-mediated activation of mast cells degranulation by PI3K/Akt/PLCγ/Ca(2+) pathway.微小RNA-221通过PI3K/Akt/PLCγ/Ca(2+)信号通路促进IgE介导的肥大细胞脱颗粒激活。
J Bioenerg Biomembr. 2016 Jun;48(3):293-9. doi: 10.1007/s10863-016-9659-7. Epub 2016 Apr 25.
5
Phosphoinositide 3-kinase-δ regulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress.磷脂酰肌醇3激酶δ通过内质网应激调节真菌诱导的过敏性肺部炎症。
Thorax. 2016 Jan;71(1):52-63. doi: 10.1136/thoraxjnl-2015-207096. Epub 2015 Nov 5.
6
Restoration of Corticosteroid Sensitivity in Chronic Obstructive Pulmonary Disease by Inhibition of Mammalian Target of Rapamycin.通过抑制雷帕霉素哺乳动物靶点恢复慢性阻塞性肺疾病中的皮质类固醇敏感性
Am J Respir Crit Care Med. 2016 Jan 15;193(2):143-53. doi: 10.1164/rccm.201503-0593OC.
7
Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle cells from asthmatic patients.小 RNA 谱分析显示哮喘患者支气管平滑肌细胞中磷酸酶和张力蛋白同源物 (PTEN)/磷酸肌醇 3-激酶 (PI3K)/Akt 通路失调。
J Allergy Clin Immunol. 2016 Jan;137(1):58-67. doi: 10.1016/j.jaci.2015.05.031. Epub 2015 Jul 3.
8
PI3K inhibitors in inflammation, autoimmunity and cancer.炎症、自身免疫和癌症中的PI3K抑制剂
Curr Opin Pharmacol. 2015 Aug;23:82-91. doi: 10.1016/j.coph.2015.05.017. Epub 2015 Jun 18.
9
Rapamycin inhibition of eosinophil differentiation attenuates allergic airway inflammation in mice.雷帕霉素抑制嗜酸性粒细胞分化可减轻小鼠过敏性气道炎症。
Respirology. 2015 Oct;20(7):1055-65. doi: 10.1111/resp.12554. Epub 2015 Jun 4.
10
Defective Resensitization in Human Airway Smooth Muscle Cells Evokes β-Adrenergic Receptor Dysfunction in Severe Asthma.人气道平滑肌细胞中再敏化缺陷引发重症哮喘中的β-肾上腺素能受体功能障碍。
PLoS One. 2015 May 29;10(5):e0125803. doi: 10.1371/journal.pone.0125803. eCollection 2015.
Zotero 插件