代谢重编程在特发性肺纤维化中的研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

王雪松 , 张廷伟 , 康弟 , 王莹莹 , 邵野 ,  李洪波

滨州医学院附属医院（第一临床医学院）呼吸与危重症医学科（山东滨州 256603）;

Corresponding author：

李洪波, Email: lihongbo0516@sina.com

Keywords：

DOI：

10.7507/1671-6205.202307056

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Citation： 王雪松, 张廷伟, 康弟, 王莹莹, 邵野, 李洪波. 代谢重编程在特发性肺纤维化中的研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2023, 22(11): 825-831. doi: 10.7507/1671-6205.202307056 Copy

1.	Lamb YN. Nintedanib: a review in fibrotic interstitial lung diseases. Drugs, 2021, 81(5): 575-586.
2.	Spagnolo P, Kropski JA, Jones MG, et al. Idiopathic pulmonary fibrosis: disease mechanisms and drug development. Pharmacol Ther, 2021, 222: 107798.
3.	Mei Q, Liu Z, Zuo H, et al. Idiopathic pulmonary fibrosis: an update on pathogenesis. Front Pharmacol, 2022, 12: 797292.
4.	Song JW, Ogura T, Inoue Y, et al. Long‐term treatment with nintedanib in Asian patients with idiopathic pulmonary fibrosis: results from INPULSIS®‐ON. Respirology, 2020, 25(4): 410-416.
5.	Pereira CA de C, Baddini-Martinez JA, Baldi BG, et al. Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil. J Bras Pneumol, 2019, 45(5): e20180414.
6.	Borok Z, Horie M, Flodby P, et al. Grp78 loss in epithelial progenitors reveals an age-linked role for endoplasmic reticulum stress in pulmonary fibrosis. Am J Respir Crit Care Med, 2020, 201(2): 198-211.
7.	Geng Y, Li L, Yan J, et al. PEAR1 regulates expansion of activated fibroblasts and deposition of extracellular matrix in pulmonary fibrosis. Nat Commun, 2022, 13: 7114.
8.	Burgoyne RA, Fisher AJ, Borthwick LA. The role of epithelial damage in the pulmonary immune response. Cells, 2021, 10(10): 2763.
9.	Redente EF, Black BP, Backos DS, et al. Persistent, progressive pulmonary fibrosis and epithelial remodeling in mice. Am J Respir Cell Mol Biol, 2021, 64(6): 669-676.
10.	Hong X, Wang L, Zhang K, et al. Molecular mechanisms of alveolar epithelial stem cell senescence and senescence-associated differentiation disorders in pulmonary fibrosis. Cells, 2022, 11(5): 877.
11.	Glass DS, Grossfeld D, Renna HA, et al. Idiopathic pulmonary fibrosis: Current and future treatment. Clin Respir J, 2022, 16(2): 84-96.
12.	Hewlett JC, Kropski JA, Blackwell TS. Idiopathic pulmonary fibrosis: epithelial-mesenchymal interactions and emerging therapeutic targets. Matrix Biol, 2018, 71-72: 112-127.
13.	Sun W, Jing X, Yang X, et al. Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation. Aging (Albany NY), 2021, 13(14): 18852-18869.
14.	Wollin L, Wex E, Pautsch A, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J, 2015, 45(5): 1434-1445.
15.	Saito S, Alkhatib A, Kolls JK, et al. Pharmacotherapy and adjunctive treatment for idiopathic pulmonary fibrosis (IPF). J Thorac Dis, 2019, 11(Suppl 14): S1740-S1754.
16.	Li JX, Zhai XX, Sun X, et al. Metabolic reprogramming of pulmonary fibrosis. Front Pharmacol, 2022, 13: 1031890.
17.	Yoshida GJ. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res, 2015, 34: 111.
18.	Zhang Y, Meng Q, Sun Q, et al. LKB1 deficiency-induced metabolic reprogramming in tumorigenesis and non-neoplastic diseases. Mol Metab, 2020, 44: 101131.
19.	Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci, 2016, 41(3): 211-218.
20.	Dai Y, Li F, Jiao YW, et al. Mortalin/glucose-regulated protein 75 promotes the cisplatin-resistance of gastric cancer via regulating anti-oxidation/apoptosis and metabolic reprogramming. Cell Death Discov, 2021, 7: 140.
21.	Honkoop H, de Bakker DE, Aharonov A, et al. Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart. eLife, 8: e50163.
22.	Zanotelli MR, Zhang J, Reinhart-King CA. Mechanoresponsive metabolism in cancer cell migration and metastasis. Cell Metab, 2021, 33(7): 1307-1321.
23.	Nelson JK, Thin MZ, Evan T, et al. USP25 promotes pathological HIF-1-driven metabolic reprogramming and is a potential therapeutic target in pancreatic cancer. Nat Commun, 2022, 13: 2070.
24.	Xiao L, Wang Q, Peng HL. Tumor-associated macrophages: new insights on their metabolic regulation and their influence in cancer immunotherapy. Front Immunol, 2023, 14: 1157291.
25.	Roque W, Romero F. Cellular metabolomics of pulmonary fibrosis, from amino acids to lipids. Am J Physiol Cell Physiol, 2021, 320(5): C689-C695.
26.	Ung CY, Onoufriadis A, Parsons M, et al. Metabolic perturbations in fibrosis disease. Int J Biochem Cell Biol, 2021, 139: 106073.
27.	Selvarajah B, Azuelos I, Anastasiou D, et al. Fibrometabolism-an emerging therapeutic frontier in pulmonary fibrosis. Sci Signal, 2021, 14(697): eaay1027.
28.	Suryadevara V, Ramchandran R, et al. Lipid mediators regulate pulmonary fibrosis: potential mechanisms and signaling pathways. Int J Mol Sci, 2020, 21(12): 4257.
29.	Chen RX, Dai JH. Lipid metabolism in idiopathic pulmonary fibrosis: from pathogenesis to therapy. J Mol Med (Berl), 2023, 101(8): 905-915.
30.	Agudelo CW, Samaha G, Garcia-Arcos I. Alveolar lipids in pulmonary disease. A review. Lipids Health Dis, 2020, 19: 122.
31.	Burgy O, Loriod S, Beltramo G, et al. Extracellular lipids in the lung and their role in pulmonary fibrosis. Cells, 2022, 11(7): 1209.
32.	Hamanaka RB, Mutlu GM. The role of metabolic reprogramming and de novo amino acid synthesis in collagen protein production by myofibroblasts: Implications for organ fibrosis and cancer. Amino Acids, 2021, 53(12): 1851-1862.
33.	Wang SS, Li X, Ma QW, et al. Glutamine metabolism is required for alveolar regeneration during lung injury. Biomolecules, 2022, 12(5): 728.
34.	Veith C, Boots AW, Idris M, et al. Redox imbalance in idiopathic pulmonary fibrosis: a role for oxidant cross-talk between NADPH oxidase enzymes and mitochondria. Antioxid Redox Signal, 2019, 31(14): 1092-1115.
35.	Caldeira D de AF, Weiss DJ, Rocco PRM, et al. Mitochondria in focus: from function to therapeutic strategies in chronic lung diseases. Front Immunol, 2021, 12: 782074.
36.	Ryter SW, Rosas IO, Owen CA, et al. Mitochondrial dysfunction as a pathogenic mediator of chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Ann Am Thorac Soc, 2018, 15(Suppl 4): S266-S272.
37.	Zhou WC, Qu J, Xie SY, et al. Mitochondrial dysfunction in chronic respiratory diseases: implications for the pathogenesis and potential therapeutics. Oxid Med Cell Longev, 2021, 2021: 5188306.
38.	Gu LL, Larson Casey JL, Andrabi SA, et al. Mitochondrial calcium uniporter regulates PGC-1α expression to mediate metabolic reprogramming in pulmonary fibrosis. Redox Biol, 2019, 26: 101307.
39.	Bargagli E, Refini RM, d’Alessandro M, et al. Metabolic dysregulation in idiopathic pulmonary fibrosis. Int J Mol Sci, 2020, 21(16): 5663.
40.	Newton DA, Lottes RG, Ryan RM, et al. Dysfunctional lactate metabolism in human alveolar type II cells from idiopathic pulmonary fibrosis lung explant tissue. Respir Res, 2021, 22: 278.
41.	Wang M, Liu AD, Niu Q, et al. Blockade of phosphotyrosine pathways suggesting SH2 superbinder as a novel therapy for pulmonary fibrosis. Theranostics, 2022, 12(10): 4513-4535.
42.	Zhang JM, Chen WM, Du JZ, et al. RNF130 protects against pulmonary fibrosis through suppressing aerobic glycolysis by mediating c-myc ubiquitination. Int Immunopharmacol, 2023, 117: 109985.
43.	Wang L, Zhu MH, Li Y, et al. Serum proteomics identifies biomarkers associated with the pathogenesis of idiopathic pulmonary fibrosis. Mol Cell Proteomics, 2023, 22(4): 100524.
44.	Rehan M, Deskin B, Kurundkar AR, et al. Nicotinamide N-methyltransferase mediates lipofibroblast-myofibroblast transition and apoptosis resistance. J Biol Chem, 2023, 299(8): 105027.
45.	Chen W, Zhang J, Zhong W, et al. Anlotinib inhibits PFKFB3-driven glycolysis in myofibroblasts to reverse pulmonary fibrosis. Front Pharmacol, 2021, 12: 744826.
46.	许琪. circHIPK3调控成纤维细胞糖酵解促进矽尘诱导肺纤维化的机制研究. 南京医科大学, 2021.
47.	Zhang Y, Li T, Pan MX, et al. SIRT1 prevents cigarette smoking-induced lung fibroblasts activation by regulating mitochondrial oxidative stress and lipid metabolism. J Transl Med, 2022, 20: 222.
48.	常美玉. α-硫辛酸调节线粒体能量代谢干预SiO_2诱导的小鼠肺纤维化作用研究. 新乡医学院, 2021.
49.	Ahangari F, Price NL, Malik S, et al. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight, 2023, 8(4): e158100.
50.	Larson-Casey JL, Vaid M, Gu L, et al. Increased flux through the mevalonate pathway mediates fibrotic repair without injury. J Clin Invest, 2019, 129(11): 4962-4978.
51.	Li QF, Cheng Y, Zhang Z, et al. Inhibition of ROCK ameliorates pulmonary fibrosis by suppressing M2 macrophage polarisation through phosphorylation of STAT3. Clin Transl Med, 2022, 12(10): e1036.

1. Lamb YN. Nintedanib: a review in fibrotic interstitial lung diseases. Drugs, 2021, 81(5): 575-586.
2. Spagnolo P, Kropski JA, Jones MG, et al. Idiopathic pulmonary fibrosis: disease mechanisms and drug development. Pharmacol Ther, 2021, 222: 107798.
3. Mei Q, Liu Z, Zuo H, et al. Idiopathic pulmonary fibrosis: an update on pathogenesis. Front Pharmacol, 2022, 12: 797292.
4. Song JW, Ogura T, Inoue Y, et al. Long‐term treatment with nintedanib in Asian patients with idiopathic pulmonary fibrosis: results from INPULSIS®‐ON. Respirology, 2020, 25(4): 410-416.
5. Pereira CA de C, Baddini-Martinez JA, Baldi BG, et al. Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil. J Bras Pneumol, 2019, 45(5): e20180414.
6. Borok Z, Horie M, Flodby P, et al. Grp78 loss in epithelial progenitors reveals an age-linked role for endoplasmic reticulum stress in pulmonary fibrosis. Am J Respir Crit Care Med, 2020, 201(2): 198-211.
7. Geng Y, Li L, Yan J, et al. PEAR1 regulates expansion of activated fibroblasts and deposition of extracellular matrix in pulmonary fibrosis. Nat Commun, 2022, 13: 7114.
8. Burgoyne RA, Fisher AJ, Borthwick LA. The role of epithelial damage in the pulmonary immune response. Cells, 2021, 10(10): 2763.
9. Redente EF, Black BP, Backos DS, et al. Persistent, progressive pulmonary fibrosis and epithelial remodeling in mice. Am J Respir Cell Mol Biol, 2021, 64(6): 669-676.
10. Hong X, Wang L, Zhang K, et al. Molecular mechanisms of alveolar epithelial stem cell senescence and senescence-associated differentiation disorders in pulmonary fibrosis. Cells, 2022, 11(5): 877.
11. Glass DS, Grossfeld D, Renna HA, et al. Idiopathic pulmonary fibrosis: Current and future treatment. Clin Respir J, 2022, 16(2): 84-96.
12. Hewlett JC, Kropski JA, Blackwell TS. Idiopathic pulmonary fibrosis: epithelial-mesenchymal interactions and emerging therapeutic targets. Matrix Biol, 2018, 71-72: 112-127.
13. Sun W, Jing X, Yang X, et al. Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation. Aging (Albany NY), 2021, 13(14): 18852-18869.
14. Wollin L, Wex E, Pautsch A, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J, 2015, 45(5): 1434-1445.
15. Saito S, Alkhatib A, Kolls JK, et al. Pharmacotherapy and adjunctive treatment for idiopathic pulmonary fibrosis (IPF). J Thorac Dis, 2019, 11(Suppl 14): S1740-S1754.
16. Li JX, Zhai XX, Sun X, et al. Metabolic reprogramming of pulmonary fibrosis. Front Pharmacol, 2022, 13: 1031890.
17. Yoshida GJ. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res, 2015, 34: 111.
18. Zhang Y, Meng Q, Sun Q, et al. LKB1 deficiency-induced metabolic reprogramming in tumorigenesis and non-neoplastic diseases. Mol Metab, 2020, 44: 101131.
19. Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci, 2016, 41(3): 211-218.
20. Dai Y, Li F, Jiao YW, et al. Mortalin/glucose-regulated protein 75 promotes the cisplatin-resistance of gastric cancer via regulating anti-oxidation/apoptosis and metabolic reprogramming. Cell Death Discov, 2021, 7: 140.
21. Honkoop H, de Bakker DE, Aharonov A, et al. Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart. eLife, 8: e50163.
22. Zanotelli MR, Zhang J, Reinhart-King CA. Mechanoresponsive metabolism in cancer cell migration and metastasis. Cell Metab, 2021, 33(7): 1307-1321.
23. Nelson JK, Thin MZ, Evan T, et al. USP25 promotes pathological HIF-1-driven metabolic reprogramming and is a potential therapeutic target in pancreatic cancer. Nat Commun, 2022, 13: 2070.
24. Xiao L, Wang Q, Peng HL. Tumor-associated macrophages: new insights on their metabolic regulation and their influence in cancer immunotherapy. Front Immunol, 2023, 14: 1157291.
25. Roque W, Romero F. Cellular metabolomics of pulmonary fibrosis, from amino acids to lipids. Am J Physiol Cell Physiol, 2021, 320(5): C689-C695.
26. Ung CY, Onoufriadis A, Parsons M, et al. Metabolic perturbations in fibrosis disease. Int J Biochem Cell Biol, 2021, 139: 106073.
27. Selvarajah B, Azuelos I, Anastasiou D, et al. Fibrometabolism-an emerging therapeutic frontier in pulmonary fibrosis. Sci Signal, 2021, 14(697): eaay1027.
28. Suryadevara V, Ramchandran R, et al. Lipid mediators regulate pulmonary fibrosis: potential mechanisms and signaling pathways. Int J Mol Sci, 2020, 21(12): 4257.
29. Chen RX, Dai JH. Lipid metabolism in idiopathic pulmonary fibrosis: from pathogenesis to therapy. J Mol Med (Berl), 2023, 101(8): 905-915.
30. Agudelo CW, Samaha G, Garcia-Arcos I. Alveolar lipids in pulmonary disease. A review. Lipids Health Dis, 2020, 19: 122.
31. Burgy O, Loriod S, Beltramo G, et al. Extracellular lipids in the lung and their role in pulmonary fibrosis. Cells, 2022, 11(7): 1209.
32. Hamanaka RB, Mutlu GM. The role of metabolic reprogramming and de novo amino acid synthesis in collagen protein production by myofibroblasts: Implications for organ fibrosis and cancer. Amino Acids, 2021, 53(12): 1851-1862.
33. Wang SS, Li X, Ma QW, et al. Glutamine metabolism is required for alveolar regeneration during lung injury. Biomolecules, 2022, 12(5): 728.
34. Veith C, Boots AW, Idris M, et al. Redox imbalance in idiopathic pulmonary fibrosis: a role for oxidant cross-talk between NADPH oxidase enzymes and mitochondria. Antioxid Redox Signal, 2019, 31(14): 1092-1115.
35. Caldeira D de AF, Weiss DJ, Rocco PRM, et al. Mitochondria in focus: from function to therapeutic strategies in chronic lung diseases. Front Immunol, 2021, 12: 782074.
36. Ryter SW, Rosas IO, Owen CA, et al. Mitochondrial dysfunction as a pathogenic mediator of chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Ann Am Thorac Soc, 2018, 15(Suppl 4): S266-S272.
37. Zhou WC, Qu J, Xie SY, et al. Mitochondrial dysfunction in chronic respiratory diseases: implications for the pathogenesis and potential therapeutics. Oxid Med Cell Longev, 2021, 2021: 5188306.
38. Gu LL, Larson Casey JL, Andrabi SA, et al. Mitochondrial calcium uniporter regulates PGC-1α expression to mediate metabolic reprogramming in pulmonary fibrosis. Redox Biol, 2019, 26: 101307.
39. Bargagli E, Refini RM, d’Alessandro M, et al. Metabolic dysregulation in idiopathic pulmonary fibrosis. Int J Mol Sci, 2020, 21(16): 5663.
40. Newton DA, Lottes RG, Ryan RM, et al. Dysfunctional lactate metabolism in human alveolar type II cells from idiopathic pulmonary fibrosis lung explant tissue. Respir Res, 2021, 22: 278.
41. Wang M, Liu AD, Niu Q, et al. Blockade of phosphotyrosine pathways suggesting SH2 superbinder as a novel therapy for pulmonary fibrosis. Theranostics, 2022, 12(10): 4513-4535.
42. Zhang JM, Chen WM, Du JZ, et al. RNF130 protects against pulmonary fibrosis through suppressing aerobic glycolysis by mediating c-myc ubiquitination. Int Immunopharmacol, 2023, 117: 109985.
43. Wang L, Zhu MH, Li Y, et al. Serum proteomics identifies biomarkers associated with the pathogenesis of idiopathic pulmonary fibrosis. Mol Cell Proteomics, 2023, 22(4): 100524.
44. Rehan M, Deskin B, Kurundkar AR, et al. Nicotinamide N-methyltransferase mediates lipofibroblast-myofibroblast transition and apoptosis resistance. J Biol Chem, 2023, 299(8): 105027.
45. Chen W, Zhang J, Zhong W, et al. Anlotinib inhibits PFKFB3-driven glycolysis in myofibroblasts to reverse pulmonary fibrosis. Front Pharmacol, 2021, 12: 744826.
46. 许琪. circHIPK3调控成纤维细胞糖酵解促进矽尘诱导肺纤维化的机制研究. 南京医科大学, 2021.
47. Zhang Y, Li T, Pan MX, et al. SIRT1 prevents cigarette smoking-induced lung fibroblasts activation by regulating mitochondrial oxidative stress and lipid metabolism. J Transl Med, 2022, 20: 222.
48. 常美玉. α-硫辛酸调节线粒体能量代谢干预SiO_2诱导的小鼠肺纤维化作用研究. 新乡医学院, 2021.
49. Ahangari F, Price NL, Malik S, et al. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight, 2023, 8(4): e158100.
50. Larson-Casey JL, Vaid M, Gu L, et al. Increased flux through the mevalonate pathway mediates fibrotic repair without injury. J Clin Invest, 2019, 129(11): 4962-4978.
51. Li QF, Cheng Y, Zhang Z, et al. Inhibition of ROCK ameliorates pulmonary fibrosis by suppressing M2 macrophage polarisation through phosphorylation of STAT3. Clin Transl Med, 2022, 12(10): e1036.

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代谢重编程在特发性肺纤维化中的研究进展

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