PI3K-Akt信号通路调控慢性阻塞性肺疾病气道炎症反应的研究新进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

梁可克 ,  王志旺 , 黄柯婷 , 庞亚蓉 , 席建宏 , 杜玥 , 李济阳

甘肃中医药大学药学院（甘肃兰州 730000）;

Corresponding author：

王志旺, Email: wzw0933@126.com

Keywords：

DOI：

10.7507/1671-6205.202206015

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Citation： 梁可克, 王志旺, 黄柯婷, 庞亚蓉, 席建宏, 杜玥, 李济阳. PI3K-Akt信号通路调控慢性阻塞性肺疾病气道炎症反应的研究新进展. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(10): 751-755. doi: 10.7507/1671-6205.202206015 Copy

1.	Zhang DW, Wei YY, Ji S, et al. Correlation between sestrin2 expression and airway remodeling in COPD. BMC Pulm Med, 2020, 20(1): 297.
2.	Moradi S, Jarrahi E, Ahmadi A, et al. PI3K signalling in chronic obstructive pulmonary disease and opportunities for therapy. J Pathol, 2021, 254(5): 505-518.
3.	Li T, Tan XQ, Huang YX, et al. MicroRNA miR-627-5p restrains pulmonary artery smooth muscle cell dysfunction by targeting MAP 2 K4 and PI3K/AKT signaling. Genes Environ, 2022, 44(1): 23.
4.	Noorolyai S, Shajari N, Baghbani E, et al. The relation between PI3K/AKT signalling pathway and cancer. Gene, 2019, 698: 120-128.
5.	Liu ZY, Huang ML, Hong Y, et al. Isovalerylspiramycin I suppresses non-small cell lung carcinoma growth through ROS-mediated inhibition of PI3K/AKT signaling pathway. Int J Biol Sci, 2022, 18(9): 3714-3730.
6.	Fujita A, Kan-O K, Tonai K, et al. Inhibition of PI3Kδ enhances Poly I:C-induced antiviral responses and inhibits replication of human metapneumovirus in murine lungs and human bronchial epithelial cells. Front Immunol, 2020, 11: 432.
7.	Begg M, Hamblin JN, Jarvis E, et al. Exploring PI3Kδ molecular pathways in stable COPD and following an acute exacerbation, two randomized controlled trials. Int J Chron Obstruct Pulmon Dis, 2021, 16: 1621-1636.
8.	Li T, Fanning KV, Nyunoya T, et al. Cigarette smoke extract induces airway epithelial cell death via repressing PRMT6/AKT signaling. Aging (Albany NY), 2020, 12(23): 24301-24317.
9.	Zhang LX, Tian YG, Zhao P, et al. Electroacupuncture attenuates pulmonary vascular remodeling in a rat model of chronic obstructive pulmonary disease via the VEGF/PI3K/Akt pathway. Acupunct Med, 2022, 40(4): 389-400.
10.	Pirozzi F, Ren K, Murabito A, et al. PI3K signaling in chronic obstructive pulmonary disease: mechanisms, targets, and therapy. Curr Med Chem, 2019, 26(16): 2791-2800.
11.	肖华叶, 梁斌苗, 欧雪梅. 中性粒细胞与淋巴细胞比值在慢性阻塞性肺疾病急性加重期中的价值. 中国呼吸与危重监护杂志, 2021, 20(2): 85-90.
12.	Saber CL, Diabasana Z, Perotin JM, et al. The nicotinic receptor polymorphism rs16969968 is associated with airway remodeling and inflammatory dysregulation in COPD patients. Cells, 2022, 11(19): 2937.
13.	江宇航, 梅晓峰, 贾利丹, 等. 香烟烟雾诱导慢性阻塞性肺疾病模型小鼠气道上皮屏障损伤的机制. 中国病理生理杂志, 2022, 38(7): 1297-1303.
14.	Cahn A, Hamblin JN, Begg M, et al. Safety, pharmacokinetics and dose-response characteristics of GSK2269557, an inhaled PI3Kδ inhibitor under development for the treatment of COPD. Pulm Pharmacol Ther, 2017, 46: 69-77.
15.	Yang Y, Huang L, Tian CC, et al. Magnesium isoglycyrrhizinate inhibits airway inflammation in rats with chronic obstructive pulmonary disease. BMC Pulm Med, 2021, 21(1): 371.
16.	Guan XW, Yuan YZ, Wang GQ, et al. Ginsenoside Rg3 ameliorates acute exacerbation of COPD by suppressing neutrophil migration. Int Immunopharmacol, 2020, 83: 106449.
17.	Gupta V, Khan A, Higham A, et al. The effect of phosphatidylinositol-3 kinase inhibition on matrix metalloproteinase-9 and reactive oxygen species release from chronic obstructive pulmonary disease neutrophils. Int immunopharmacol, 2016, 35: 155-162.
18.	So L, Fruman DA. PI3K signalling in B-and T-lymphocytes: new developments and therapeutic advances. Biochem J, 2012, 442(3): 465-481.
19.	Su JC, Zhang Y, Cheng C, et al. Hydrogen regulates the M1/M2 polarization of alveolar macrophages in a rat model of chronic obstructive pulmonary disease. Exp Lung Res, 2021, 47(7): 301-310.
20.	Sriskantharajah S, Hamblin N, Worsley S, et al. Targeting phosphoinositide 3-kinase delta for the treatment of respiratory diseases. Ann N Y Acad Sci, 2013, 1280(1): 35-39.
21.	Jamal Jameel K, Gallert WJ, Yanik SD, et al. Biomarkers for comorbidities modulate the activity of T-Cells in COPD. Int J Mol Sci, 2021, 22(13): 7187.
22.	Xu WH, Li RM, Sun YC. Increased IFN-γ-producing Th17/Th1 cells and their association with lung function and current smoking status in patients with chronic obstructive pulmonary disease. BMC Pulm Med, 2019, 19(1): 137.
23.	Khan A, Southworth T, Worsley S, et al. An investigation of the anti-inflammatory effects and a potential biomarker of PI3Kδ inhibition in COPD T cells. Clin Exp Pharmacol Physiol, 2017, 44(9): 932-940.
24.	Li H, Song S, Kong Zb, et al. Regulatory effects of andrographolide on lung tissue inflammation and Th17/Treg in rats with chronic obstructive pulmonary disease induced by smoking and lipopolysaccharide. J Biomater Tiss Eng, 2021, 11(3): 513-519.
25.	何燚, 伍晓玲, 陈晓婷. 白细胞介素-17在慢性阻塞性肺疾病患者中的表达及作用机制. 免疫学杂志, 2019, 35(4): 341-347, 355.
26.	陈忠仁, 欧宗兴, 王蕾, 等. PI3K信号通路在慢性阻塞性肺疾病大鼠气道及系统性炎症中的作用. 中国老年学杂志, 2020, 40(23): 5032-5035.
27.	Li Z, He PY, Ding HW, et al. Association between peripheral blood WBCs C3aR mRNA level and plasma C3a, C3aR, IL-1β concentrations and acute exacerbation of chronic obstructive pulmonary disease. Immunobiology, 2022, 227(1): 152164.
28.	Yu H, Lin LB, Zhang ZQ, et al. Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther, 2020, 5(1): 209.
29.	Yang LL, Wen MY, Liu XH, et al. Feikang granules ameliorate pulmonary inflammation in the rat model of chronic obstructive pulmonary disease via TLR2/4-mediated NF-κB pathway. BMC Complement Med Ther, 2020, 20(1): 170.
30.	Tan HT, Liu LL, Chen JX, et al. Yiqi Huoxue Huatan formula attenuates inflammation in chronic obstructive pulmonary disease by suppressing the activation of PI3K/AKT and NF-κB signaling pathways. Trop J Pharm Res, 2022, 21(1): 45-52.
31.	Xie YP, He QX, Chen H, et al. Crocin ameliorates chronic obstructive pulmonary disease-induced depression via PI3K/Akt mediated suppression of inflammation. Eur J Pharmacol, 2019, 862: 172640.
32.	刘瑞, 郑红刚, 李卫东, 等. 肺瘤平膏及其联合不同类别药物对肺转移微环境中PI3K/AKT/NF-κB表达的研究. 中国中药杂志, 2018, 43(19): 3913-3918.
33.	唐艺玲, 张培蓓, 叶贤伟. PI3K-Akt-mTOR通路在慢阻肺发病机制中的研究进展. 中国现代医生, 2021, 59(18): 178-183.
34.	李敏静, 陈晔, 蔡宛如, 等. 温肾益气颗粒对慢性阻塞性肺疾病大鼠气道平滑肌细胞增殖及PI3K/AKT/mTOR信号通路表达的影响. 中华中医药杂志, 2019, 34(4): 1711-1714.
35.	Wang L, Jiang WZ, Wang J, et al. Puerarin inhibits FUNDC1-mediated mitochondrial autophagy and CSE-induced apoptosis of human bronchial epithelial cells by activating the PI3K/AKT/mTOR signaling pathway. Aging (Albany NY), 2022, 14(3): 1253-1264.
36.	李晓丹, 王强. 补肺颗粒通过调控Akt通路对慢阻肺大鼠肺组织自噬和凋亡的影响. 武汉大学学报(医学版), 2020, 41(6): 904-910, 916.
37.	Zhang F, Ma H, Wang ZL, et al. The PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in chronic obstructive pulmonary disease caused by PM2.5 particulate matter. J Int Med Res, 2020, 48(7): 300060520927919.
38.	Taniguchi A, Tsuge M, Miyahara N, et al. Reactive oxygen species and antioxidative defense in chronic obstructive pulmonary disease. Antioxidants (Basel), 2021, 10(10): 1537.
39.	谭春婷, 王浩彦. 组蛋白去乙酰化酶2与慢性阻塞性肺疾病. 中国呼吸与危重监护杂志, 2015, 14(4): 410-413.
40.	Ho CY, Weng CJ, Jhang JJ, et al. Diallyl sulfide as a potential dietary agent to reduce TNF‐α‐and histamine‐induced proinflammatory responses in A7r5 cells. Mol Nutr Food Res, 2014, 58(5): 1069-1078.
41.	Sun XJ, Li ZH, Zhang Y, et al. Combination of erythromycin and dexamethasone improves corticosteroid sensitivity induced by CSE through inhibiting PI3K-δ/Akt pathway and increasing GR expression. Am J Physiol Lung Cell Mol Physiol, 2015, 309(2): L139-L146.
42.	Barnes PJ. Oxidative stress-based therapeutics in COPD. Redox Biol, 2020, 33: 101544.
43.	Lee KH, Lee CH, Woo J, et al. Cigarette smoke extract enhances IL-17A-induced IL-8 production via up-regulation of IL-17R in human bronchial epithelial cells. Mol Cells, 2018, 41(4): 282-289.
44.	Yanagisawa S, Baker JR, Vuppusetty C, et al. Decreased phosphatase PTEN amplifies PI3K signaling and enhances proinflammatory cytokine release in COPD. Am J Physiol Lung Cell Mol Physiol, 2017, 313(2): L230-L239.
45.	Zhang HX, Yang JJ, Zhang SA, et al. HIF-1α promotes inflammatory response of chronic obstructive pulmonary disease by activating EGFR/PI3K/AKT pathway. Eur Rev Med Pharmacol Sci, 2018, 22(18): 6077-6084.

1. Zhang DW, Wei YY, Ji S, et al. Correlation between sestrin2 expression and airway remodeling in COPD. BMC Pulm Med, 2020, 20(1): 297.
2. Moradi S, Jarrahi E, Ahmadi A, et al. PI3K signalling in chronic obstructive pulmonary disease and opportunities for therapy. J Pathol, 2021, 254(5): 505-518.
3. Li T, Tan XQ, Huang YX, et al. MicroRNA miR-627-5p restrains pulmonary artery smooth muscle cell dysfunction by targeting MAP 2 K4 and PI3K/AKT signaling. Genes Environ, 2022, 44(1): 23.
4. Noorolyai S, Shajari N, Baghbani E, et al. The relation between PI3K/AKT signalling pathway and cancer. Gene, 2019, 698: 120-128.
5. Liu ZY, Huang ML, Hong Y, et al. Isovalerylspiramycin I suppresses non-small cell lung carcinoma growth through ROS-mediated inhibition of PI3K/AKT signaling pathway. Int J Biol Sci, 2022, 18(9): 3714-3730.
6. Fujita A, Kan-O K, Tonai K, et al. Inhibition of PI3Kδ enhances Poly I:C-induced antiviral responses and inhibits replication of human metapneumovirus in murine lungs and human bronchial epithelial cells. Front Immunol, 2020, 11: 432.
7. Begg M, Hamblin JN, Jarvis E, et al. Exploring PI3Kδ molecular pathways in stable COPD and following an acute exacerbation, two randomized controlled trials. Int J Chron Obstruct Pulmon Dis, 2021, 16: 1621-1636.
8. Li T, Fanning KV, Nyunoya T, et al. Cigarette smoke extract induces airway epithelial cell death via repressing PRMT6/AKT signaling. Aging (Albany NY), 2020, 12(23): 24301-24317.
9. Zhang LX, Tian YG, Zhao P, et al. Electroacupuncture attenuates pulmonary vascular remodeling in a rat model of chronic obstructive pulmonary disease via the VEGF/PI3K/Akt pathway. Acupunct Med, 2022, 40(4): 389-400.
10. Pirozzi F, Ren K, Murabito A, et al. PI3K signaling in chronic obstructive pulmonary disease: mechanisms, targets, and therapy. Curr Med Chem, 2019, 26(16): 2791-2800.
11. 肖华叶, 梁斌苗, 欧雪梅. 中性粒细胞与淋巴细胞比值在慢性阻塞性肺疾病急性加重期中的价值. 中国呼吸与危重监护杂志, 2021, 20(2): 85-90.
12. Saber CL, Diabasana Z, Perotin JM, et al. The nicotinic receptor polymorphism rs16969968 is associated with airway remodeling and inflammatory dysregulation in COPD patients. Cells, 2022, 11(19): 2937.
13. 江宇航, 梅晓峰, 贾利丹, 等. 香烟烟雾诱导慢性阻塞性肺疾病模型小鼠气道上皮屏障损伤的机制. 中国病理生理杂志, 2022, 38(7): 1297-1303.
14. Cahn A, Hamblin JN, Begg M, et al. Safety, pharmacokinetics and dose-response characteristics of GSK2269557, an inhaled PI3Kδ inhibitor under development for the treatment of COPD. Pulm Pharmacol Ther, 2017, 46: 69-77.
15. Yang Y, Huang L, Tian CC, et al. Magnesium isoglycyrrhizinate inhibits airway inflammation in rats with chronic obstructive pulmonary disease. BMC Pulm Med, 2021, 21(1): 371.
16. Guan XW, Yuan YZ, Wang GQ, et al. Ginsenoside Rg3 ameliorates acute exacerbation of COPD by suppressing neutrophil migration. Int Immunopharmacol, 2020, 83: 106449.
17. Gupta V, Khan A, Higham A, et al. The effect of phosphatidylinositol-3 kinase inhibition on matrix metalloproteinase-9 and reactive oxygen species release from chronic obstructive pulmonary disease neutrophils. Int immunopharmacol, 2016, 35: 155-162.
18. So L, Fruman DA. PI3K signalling in B-and T-lymphocytes: new developments and therapeutic advances. Biochem J, 2012, 442(3): 465-481.
19. Su JC, Zhang Y, Cheng C, et al. Hydrogen regulates the M1/M2 polarization of alveolar macrophages in a rat model of chronic obstructive pulmonary disease. Exp Lung Res, 2021, 47(7): 301-310.
20. Sriskantharajah S, Hamblin N, Worsley S, et al. Targeting phosphoinositide 3-kinase delta for the treatment of respiratory diseases. Ann N Y Acad Sci, 2013, 1280(1): 35-39.
21. Jamal Jameel K, Gallert WJ, Yanik SD, et al. Biomarkers for comorbidities modulate the activity of T-Cells in COPD. Int J Mol Sci, 2021, 22(13): 7187.
22. Xu WH, Li RM, Sun YC. Increased IFN-γ-producing Th17/Th1 cells and their association with lung function and current smoking status in patients with chronic obstructive pulmonary disease. BMC Pulm Med, 2019, 19(1): 137.
23. Khan A, Southworth T, Worsley S, et al. An investigation of the anti-inflammatory effects and a potential biomarker of PI3Kδ inhibition in COPD T cells. Clin Exp Pharmacol Physiol, 2017, 44(9): 932-940.
24. Li H, Song S, Kong Zb, et al. Regulatory effects of andrographolide on lung tissue inflammation and Th17/Treg in rats with chronic obstructive pulmonary disease induced by smoking and lipopolysaccharide. J Biomater Tiss Eng, 2021, 11(3): 513-519.
25. 何燚, 伍晓玲, 陈晓婷. 白细胞介素-17在慢性阻塞性肺疾病患者中的表达及作用机制. 免疫学杂志, 2019, 35(4): 341-347, 355.
26. 陈忠仁, 欧宗兴, 王蕾, 等. PI3K信号通路在慢性阻塞性肺疾病大鼠气道及系统性炎症中的作用. 中国老年学杂志, 2020, 40(23): 5032-5035.
27. Li Z, He PY, Ding HW, et al. Association between peripheral blood WBCs C3aR mRNA level and plasma C3a, C3aR, IL-1β concentrations and acute exacerbation of chronic obstructive pulmonary disease. Immunobiology, 2022, 227(1): 152164.
28. Yu H, Lin LB, Zhang ZQ, et al. Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther, 2020, 5(1): 209.
29. Yang LL, Wen MY, Liu XH, et al. Feikang granules ameliorate pulmonary inflammation in the rat model of chronic obstructive pulmonary disease via TLR2/4-mediated NF-κB pathway. BMC Complement Med Ther, 2020, 20(1): 170.
30. Tan HT, Liu LL, Chen JX, et al. Yiqi Huoxue Huatan formula attenuates inflammation in chronic obstructive pulmonary disease by suppressing the activation of PI3K/AKT and NF-κB signaling pathways. Trop J Pharm Res, 2022, 21(1): 45-52.
31. Xie YP, He QX, Chen H, et al. Crocin ameliorates chronic obstructive pulmonary disease-induced depression via PI3K/Akt mediated suppression of inflammation. Eur J Pharmacol, 2019, 862: 172640.
32. 刘瑞, 郑红刚, 李卫东, 等. 肺瘤平膏及其联合不同类别药物对肺转移微环境中PI3K/AKT/NF-κB表达的研究. 中国中药杂志, 2018, 43(19): 3913-3918.
33. 唐艺玲, 张培蓓, 叶贤伟. PI3K-Akt-mTOR通路在慢阻肺发病机制中的研究进展. 中国现代医生, 2021, 59(18): 178-183.
34. 李敏静, 陈晔, 蔡宛如, 等. 温肾益气颗粒对慢性阻塞性肺疾病大鼠气道平滑肌细胞增殖及PI3K/AKT/mTOR信号通路表达的影响. 中华中医药杂志, 2019, 34(4): 1711-1714.
35. Wang L, Jiang WZ, Wang J, et al. Puerarin inhibits FUNDC1-mediated mitochondrial autophagy and CSE-induced apoptosis of human bronchial epithelial cells by activating the PI3K/AKT/mTOR signaling pathway. Aging (Albany NY), 2022, 14(3): 1253-1264.
36. 李晓丹, 王强. 补肺颗粒通过调控Akt通路对慢阻肺大鼠肺组织自噬和凋亡的影响. 武汉大学学报(医学版), 2020, 41(6): 904-910, 916.
37. Zhang F, Ma H, Wang ZL, et al. The PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in chronic obstructive pulmonary disease caused by PM2.5 particulate matter. J Int Med Res, 2020, 48(7): 300060520927919.
38. Taniguchi A, Tsuge M, Miyahara N, et al. Reactive oxygen species and antioxidative defense in chronic obstructive pulmonary disease. Antioxidants (Basel), 2021, 10(10): 1537.
39. 谭春婷, 王浩彦. 组蛋白去乙酰化酶2与慢性阻塞性肺疾病. 中国呼吸与危重监护杂志, 2015, 14(4): 410-413.
40. Ho CY, Weng CJ, Jhang JJ, et al. Diallyl sulfide as a potential dietary agent to reduce TNF‐α‐and histamine‐induced proinflammatory responses in A7r5 cells. Mol Nutr Food Res, 2014, 58(5): 1069-1078.
41. Sun XJ, Li ZH, Zhang Y, et al. Combination of erythromycin and dexamethasone improves corticosteroid sensitivity induced by CSE through inhibiting PI3K-δ/Akt pathway and increasing GR expression. Am J Physiol Lung Cell Mol Physiol, 2015, 309(2): L139-L146.
42. Barnes PJ. Oxidative stress-based therapeutics in COPD. Redox Biol, 2020, 33: 101544.
43. Lee KH, Lee CH, Woo J, et al. Cigarette smoke extract enhances IL-17A-induced IL-8 production via up-regulation of IL-17R in human bronchial epithelial cells. Mol Cells, 2018, 41(4): 282-289.
44. Yanagisawa S, Baker JR, Vuppusetty C, et al. Decreased phosphatase PTEN amplifies PI3K signaling and enhances proinflammatory cytokine release in COPD. Am J Physiol Lung Cell Mol Physiol, 2017, 313(2): L230-L239.
45. Zhang HX, Yang JJ, Zhang SA, et al. HIF-1α promotes inflammatory response of chronic obstructive pulmonary disease by activating EGFR/PI3K/AKT pathway. Eur Rev Med Pharmacol Sci, 2018, 22(18): 6077-6084.

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Chinese Journal of Respiratory and Critical Care Medicine

PI3K-Akt信号通路调控慢性阻塞性肺疾病气道炎症反应的研究新进展

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