良性氣道狹窄的分子機制研究進展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

XU Chengfei , CHEN Yilin , SHI Hui ,  BAI Chong

海軍軍醫大學第一附屬醫院呼吸與危重癥醫學科（上海 200433）;

Corresponding?author：

BAI Chong, Email: bc7878@sohu.com

Keywords：

DOI：

10.7507/1671-6205.202309013

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Citation： XU Chengfei, CHEN Yilin, SHI Hui, BAI Chong. 良性氣道狹窄的分子機制研究進展. Chinese Journal of Respiratory and Critical Care Medicine, 2024, 23(4): 300-304. doi: 10.7507/1671-6205.202309013 Copy

1.	Hall SR, Allen CT, Merati AL, et al. Evaluating the utility of serological testing in laryngotracheal stenosis. Laryngoscope, 2017, 127(6): 1408-1412.
2.	Kendall RT, Feghali-Bostwick CA. Fibroblasts in fibrosis: novel roles and mediators. Front Pharmacol, 2014, 5: 123.
3.	Hinz B, Phan SH, Thannickal VJ, et al. The myofibroblast: one function, multiple origins. Am J Pathol, 2007, 170(6): 1807-1816.
4.	Evans RA, Tian YC, Steadman R, et al. TGF- 1-mediated fibroblast-myofibroblast terminal differentiation-the role of Smad proteins. Exp Cell Res, 2003, 282(2): 90-100.
5.	Gilbert RWD, Vickaryous MK, Viloria-Petit AM. Signalling by Transforming Growth Factor Beta Isoforms in Wound Healing and Tissue Regeneration. Dev Biol, 2016, 4(2): 21.
6.	PlatéM, Guillotin D, Chambers RC. The promise of mTOR as a therapeutic target pathway in idiopathic pulmonary fibrosis. Eur Respir Rev, 2020, 29(157): 200269.
7.	Hinz B, Lagares D. Evasion of apoptosis by myofibroblasts: A hallmark of fibrotic diseases. Nat Rev Rheumatol, 2020, 16(1): 11-31.
8.	Dillard DG, Gal AA, White S, et al. Transforming Growth Factor and Neutralizing Antibodies in Subglottic Stenosis. Ann Otol Rhinol Laryngol, 2001, 110(5 Pt 1): 393-400.
9.	Karagiannidis C, Velehorschi V, Obertrifter B, et al. High-level expression of matrix-associated transforming growth factor-beta 1 in benign airway stenosis. Chest, 2006, 129(5): 1298-1304.
10.	Fang S, Pentinmikko N, Ilmonen M, et al. Dual action of tgf-beta induces vascular growth in vivo through recruitment of angiogenic vegf-producing hematopoietic effector cells. Angiogenesis, 2012, 15(3): 511-519.
11.	楊平, 吳志宏, 黃靜, 等. 氧化苦參堿通過TGF-β-Smad信號通路調控人增生性瘢痕成纖維細胞增殖及功能. 中國美容整形外科雜志, 2010, 9: 557-559.
12.	Yu C, Azuma A, Li Y, et al. EM703, a new derivative of erythromycin, inhibits transforming growth factor-beta signaling in human lung fibroblasts. Exp Lung Res, 2008, 34(6): 343-354.
13.	Lee YC, Hung MH, Liu LY, et al. The roles of transforming growth factor-β1 and vascular endothelial growth factor in the tracheal granulation formation. Pulm Pharmacol Ther, 2011, 24(1): 23-31.
14.	肖陽寶, 柳廣南, 周磊, 等. 組蛋白去乙酰化酶2在結核性氣道狹窄組織中的表達. 實用預防醫學, 2020, 2: 240-243.
15.	Wernig G, Chen SY, Cui L, et al. Unifying mechanism for different fibrotic diseases. Proc Natl Acad Sci USA, 2017, 114(18): 4757-4762.
16.	Chao MP, Alizadeh AA, Tang C, et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell, 2010, 142(5): 699-713.
17.	Xue C, Hong LL, Lin JS, et al. β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway. Biosci Rep, 2018, 38(2): BSR20171386.
18.	Gu L, Li A, Lin J, et al. Knockdown of SOX9 alleviates tracheal fibrosis through the Wnt/β-catenin signaling pathway. J Mol Med (Berl), 2022, 100(11): 1659-1670.
19.	王秋瓊, 熊弢, 陳江勇, 等. SOX9 通過 Wnt /β-catenin 途徑驅動非小細胞肺癌 A549 細胞的上皮-間充質轉化. 中國腫瘤生物治療雜志, 2019, 26(12): 1345-1349.
20.	Russo RC, Garcia CC, Barcelos LS, et al. Phosphoinositide 3-kinase gamma plays a critical role in bleomycin-induced pulmonary inflammation and fibrosis in mice. J Leukoc Biol, 2011, 89(2): 269-282.
21.	Selvarajah B, Azuelos I, Platé M, et al. mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-beta1-induced collagen biosynthesis. Sci Signal, 2019, 12(582): eaav3048.
22.	Sandulache V, Parekh A, Li-Korotky H, et al. Prostaglandin E2 inhibitionofkeloid fibroblast migration, contraction, and transforming growth factor (TGF)-beta 1-induced collagen synthesis. Wound Repair Regen, 2007, 15(1): 122-133.
23.	Lina I, Tsai H, Ding D, et al. Characterization of Fibroblasts in Iatrogenic Laryngotracheal Stenosis and Type II Diabetes Mellitus. Laryngoscope, 2021, 131(7): 1570-1577.
24.	Lina IA, Berges A, Ospino R, et al. Identifying Phenotypically Distinct Fibroblast Subsets in Type 2 Diabetes-Associated Iatrogenic Laryngotracheal Stenosis. Otolaryngol Head Neck Surg, 2022, 166(4): 712-719.
25.	Sinacori JT, Taliercio SJ, Duong E, et al. Modalities of treatment for 31laryngotracheal stenosis: the EVMS experience. Laryngoscope, 2013, 123(12): 3131-3136.
26.	Gelbard A, Katsantonis NG, Mizuta M, et al. Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis. Laryngoscope, 2016, 126(11): E356-E361.
27.	Ghosh A, Malaisrie N, Leahy KP, et al. Cellular Adaptive Inflammation Mediates Airway Granulation in a Murine Model of Subglottic Stenosis. Otolaryngol Head Neck Surg, 2011, 144(6): 927-933.
28.	Hillel AT, Ding D, Samad I, et al. T-Helper 2 Lymphocyte Immunophenotype Is Associated With Iatrogenic Laryngotracheal Stenosis. Laryngoscope, 2019, 129(1): 177-186.
29.	Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies. Nat Rev Immunol, 2015, 15(5): 271-282.
30.	Sandler NG, Mentink-Kane MM, Cheever AW, Wynn TA. Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for TH1 and TH2 responses in tissue repair. J Immunol, 2003, 171(7): 3655-3667.
31.	Joshi S, Singh AR, Wong SS, et al. Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype. PLoS One, 2017, 12(8): e0182851.
32.	Motz K, Lina I, Murphy MK, et al. M2 Macrophages Promote Collagen Expression and Synthesis in Laryngotracheal Stenosis Fibroblasts. Laryngoscope, 2021, 131(2): E346-E353.
33.	Morrison RJ, Katsantonis NG, Motz KM, et al. Pathologic Fibroblasts in Idiopathic Subglottic Stenosis Amplify Local Inflammatory Signals. Otolaryngol Head Neck Surg, 2019, 160(1): 107-115.
34.	Motz KM, Yin LX, Samad I, et al. Quantification of Inflammatory Markers in Laryngotracheal Stenosis. Otolaryngol Head Neck Surg, 2017, 157(3): 466-472.
35.	Le TT, Karmouty-Quintana H, Melicoff E, et al. Blockade of IL-6 Trans signaling attenuates pulmonary fibrosis. J Immunol, 2014, 193(7): 3755-3768.
36.	Yin LX, Motz KM, Samad I, et al. Fibroblasts in Hypoxic Conditions Mimic Laryngotracheal Stenosis. Otolaryngol Head Neck Surg, 2017, 156(5): 886-892.
37.	Arellano-Orden E, Serrano C, Montes-Worboys A, et al. Stent-induced tracheal stenosis can be predicted by IL-8 expression in rabbits. Eur J Clin Invest, 2017, 47(1): 84-92.
38.	Darby IA, Hewitson TD. Hypoxia in tissue repair and fibrosis. Cell Tissue Res, 2016, 365(3): 553-562.
39.	Goodwin J, Choi H, Hsieh MH, et al. Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis. Am J Respir Cell Mol Biol, 2018, 58(2): 216-231.
40.	Cai Z, Li H, Zhang H, et al. Novel insights into the role of hypoxia-inducible factor-1 in the pathogenesis of human post-intubation tracheal stenosis. Mol Med Rep, 2013, 8(3): 903-908.
41.	Braun NA, Celada LJ, Herazo-Maya JD, et al. Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+T-Cell Proliferative Capacity. Am J Respir Crit Care Med, 2014, 190(5): 560-571.
42.	Celada LJ, Kropski JA, Herazo-Maya JD, et al. PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production. Sci Transl Med, 2018, 10(460): eaar8356.
43.	Davis RJ, Lina I, Ding D, et al. Increased Expression of PD-1 and PD-L1 in Patients With Laryngotracheal Stenosis. Laryngoscope, 2021, 131(5): 967-974.
44.	Liao J, Gan Y, Peng M, et al. GDF15 alleviates the progression of benign tracheobronchial stenosis by inhibiting epithelial-mesenchymal transition and inactivating fibroblasts. Exp Cell Res, 2022, 421(2): 113410.

1. Hall SR, Allen CT, Merati AL, et al. Evaluating the utility of serological testing in laryngotracheal stenosis. Laryngoscope, 2017, 127(6): 1408-1412.
2. Kendall RT, Feghali-Bostwick CA. Fibroblasts in fibrosis: novel roles and mediators. Front Pharmacol, 2014, 5: 123.
3. Hinz B, Phan SH, Thannickal VJ, et al. The myofibroblast: one function, multiple origins. Am J Pathol, 2007, 170(6): 1807-1816.
4. Evans RA, Tian YC, Steadman R, et al. TGF- 1-mediated fibroblast-myofibroblast terminal differentiation-the role of Smad proteins. Exp Cell Res, 2003, 282(2): 90-100.
5. Gilbert RWD, Vickaryous MK, Viloria-Petit AM. Signalling by Transforming Growth Factor Beta Isoforms in Wound Healing and Tissue Regeneration. Dev Biol, 2016, 4(2): 21.
6. PlatéM, Guillotin D, Chambers RC. The promise of mTOR as a therapeutic target pathway in idiopathic pulmonary fibrosis. Eur Respir Rev, 2020, 29(157): 200269.
7. Hinz B, Lagares D. Evasion of apoptosis by myofibroblasts: A hallmark of fibrotic diseases. Nat Rev Rheumatol, 2020, 16(1): 11-31.
8. Dillard DG, Gal AA, White S, et al. Transforming Growth Factor and Neutralizing Antibodies in Subglottic Stenosis. Ann Otol Rhinol Laryngol, 2001, 110(5 Pt 1): 393-400.
9. Karagiannidis C, Velehorschi V, Obertrifter B, et al. High-level expression of matrix-associated transforming growth factor-beta 1 in benign airway stenosis. Chest, 2006, 129(5): 1298-1304.
10. Fang S, Pentinmikko N, Ilmonen M, et al. Dual action of tgf-beta induces vascular growth in vivo through recruitment of angiogenic vegf-producing hematopoietic effector cells. Angiogenesis, 2012, 15(3): 511-519.
11. 楊平, 吳志宏, 黃靜, 等. 氧化苦參堿通過TGF-β-Smad信號通路調控人增生性瘢痕成纖維細胞增殖及功能. 中國美容整形外科雜志, 2010, 9: 557-559.
12. Yu C, Azuma A, Li Y, et al. EM703, a new derivative of erythromycin, inhibits transforming growth factor-beta signaling in human lung fibroblasts. Exp Lung Res, 2008, 34(6): 343-354.
13. Lee YC, Hung MH, Liu LY, et al. The roles of transforming growth factor-β1 and vascular endothelial growth factor in the tracheal granulation formation. Pulm Pharmacol Ther, 2011, 24(1): 23-31.
14. 肖陽寶, 柳廣南, 周磊, 等. 組蛋白去乙酰化酶2在結核性氣道狹窄組織中的表達. 實用預防醫學, 2020, 2: 240-243.
15. Wernig G, Chen SY, Cui L, et al. Unifying mechanism for different fibrotic diseases. Proc Natl Acad Sci USA, 2017, 114(18): 4757-4762.
16. Chao MP, Alizadeh AA, Tang C, et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell, 2010, 142(5): 699-713.
17. Xue C, Hong LL, Lin JS, et al. β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway. Biosci Rep, 2018, 38(2): BSR20171386.
18. Gu L, Li A, Lin J, et al. Knockdown of SOX9 alleviates tracheal fibrosis through the Wnt/β-catenin signaling pathway. J Mol Med (Berl), 2022, 100(11): 1659-1670.
19. 王秋瓊, 熊弢, 陳江勇, 等. SOX9 通過 Wnt /β-catenin 途徑驅動非小細胞肺癌 A549 細胞的上皮-間充質轉化. 中國腫瘤生物治療雜志, 2019, 26(12): 1345-1349.
20. Russo RC, Garcia CC, Barcelos LS, et al. Phosphoinositide 3-kinase gamma plays a critical role in bleomycin-induced pulmonary inflammation and fibrosis in mice. J Leukoc Biol, 2011, 89(2): 269-282.
21. Selvarajah B, Azuelos I, Platé M, et al. mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-beta1-induced collagen biosynthesis. Sci Signal, 2019, 12(582): eaav3048.
22. Sandulache V, Parekh A, Li-Korotky H, et al. Prostaglandin E2 inhibitionofkeloid fibroblast migration, contraction, and transforming growth factor (TGF)-beta 1-induced collagen synthesis. Wound Repair Regen, 2007, 15(1): 122-133.
23. Lina I, Tsai H, Ding D, et al. Characterization of Fibroblasts in Iatrogenic Laryngotracheal Stenosis and Type II Diabetes Mellitus. Laryngoscope, 2021, 131(7): 1570-1577.
24. Lina IA, Berges A, Ospino R, et al. Identifying Phenotypically Distinct Fibroblast Subsets in Type 2 Diabetes-Associated Iatrogenic Laryngotracheal Stenosis. Otolaryngol Head Neck Surg, 2022, 166(4): 712-719.
25. Sinacori JT, Taliercio SJ, Duong E, et al. Modalities of treatment for 31laryngotracheal stenosis: the EVMS experience. Laryngoscope, 2013, 123(12): 3131-3136.
26. Gelbard A, Katsantonis NG, Mizuta M, et al. Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis. Laryngoscope, 2016, 126(11): E356-E361.
27. Ghosh A, Malaisrie N, Leahy KP, et al. Cellular Adaptive Inflammation Mediates Airway Granulation in a Murine Model of Subglottic Stenosis. Otolaryngol Head Neck Surg, 2011, 144(6): 927-933.
28. Hillel AT, Ding D, Samad I, et al. T-Helper 2 Lymphocyte Immunophenotype Is Associated With Iatrogenic Laryngotracheal Stenosis. Laryngoscope, 2019, 129(1): 177-186.
29. Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies. Nat Rev Immunol, 2015, 15(5): 271-282.
30. Sandler NG, Mentink-Kane MM, Cheever AW, Wynn TA. Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for TH1 and TH2 responses in tissue repair. J Immunol, 2003, 171(7): 3655-3667.
31. Joshi S, Singh AR, Wong SS, et al. Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype. PLoS One, 2017, 12(8): e0182851.
32. Motz K, Lina I, Murphy MK, et al. M2 Macrophages Promote Collagen Expression and Synthesis in Laryngotracheal Stenosis Fibroblasts. Laryngoscope, 2021, 131(2): E346-E353.
33. Morrison RJ, Katsantonis NG, Motz KM, et al. Pathologic Fibroblasts in Idiopathic Subglottic Stenosis Amplify Local Inflammatory Signals. Otolaryngol Head Neck Surg, 2019, 160(1): 107-115.
34. Motz KM, Yin LX, Samad I, et al. Quantification of Inflammatory Markers in Laryngotracheal Stenosis. Otolaryngol Head Neck Surg, 2017, 157(3): 466-472.
35. Le TT, Karmouty-Quintana H, Melicoff E, et al. Blockade of IL-6 Trans signaling attenuates pulmonary fibrosis. J Immunol, 2014, 193(7): 3755-3768.
36. Yin LX, Motz KM, Samad I, et al. Fibroblasts in Hypoxic Conditions Mimic Laryngotracheal Stenosis. Otolaryngol Head Neck Surg, 2017, 156(5): 886-892.
37. Arellano-Orden E, Serrano C, Montes-Worboys A, et al. Stent-induced tracheal stenosis can be predicted by IL-8 expression in rabbits. Eur J Clin Invest, 2017, 47(1): 84-92.
38. Darby IA, Hewitson TD. Hypoxia in tissue repair and fibrosis. Cell Tissue Res, 2016, 365(3): 553-562.
39. Goodwin J, Choi H, Hsieh MH, et al. Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis. Am J Respir Cell Mol Biol, 2018, 58(2): 216-231.
40. Cai Z, Li H, Zhang H, et al. Novel insights into the role of hypoxia-inducible factor-1 in the pathogenesis of human post-intubation tracheal stenosis. Mol Med Rep, 2013, 8(3): 903-908.
41. Braun NA, Celada LJ, Herazo-Maya JD, et al. Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+T-Cell Proliferative Capacity. Am J Respir Crit Care Med, 2014, 190(5): 560-571.
42. Celada LJ, Kropski JA, Herazo-Maya JD, et al. PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production. Sci Transl Med, 2018, 10(460): eaar8356.
43. Davis RJ, Lina I, Ding D, et al. Increased Expression of PD-1 and PD-L1 in Patients With Laryngotracheal Stenosis. Laryngoscope, 2021, 131(5): 967-974.
44. Liao J, Gan Y, Peng M, et al. GDF15 alleviates the progression of benign tracheobronchial stenosis by inhibiting epithelial-mesenchymal transition and inactivating fibroblasts. Exp Cell Res, 2022, 421(2): 113410.

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良性氣道狹窄的分子機制研究進展

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