Ⅰ類組蛋白去乙酰化酶在肺纖維化中的研究進展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

陳丹妮 ,  向菲

華中科技大學同濟醫學院附屬協和醫院呼吸與危重癥醫學科（湖北武漢 430000）;

Corresponding?author：

向菲, Email: 2006XH0855@hust.edu.cn

Keywords：

DOI：

10.7507/1671-6205.202502050

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Citation： 陳丹妮, 向菲. Ⅰ類組蛋白去乙酰化酶在肺纖維化中的研究進展. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(11): 831-836. doi: 10.7507/1671-6205.202502050 Copy

1.	Koudstaal T, Funke-Chambour M, Kreuter M, et al. Pulmonary fibrosis: from pathogenesis to clinical decision-making. Trends Mol Med, 2023, 29(12): 1076-1087.
2.	Ahmad S, Zhang XL, Ahmad A. Epigenetic regulation of pulmonary inflammation. Semin Cell Dev Biol, 2024, 154: 346-354.
3.	Lawlor L, Yang XB. Harnessing the HDAC-histone deacetylase enzymes, inhibitors and how these can be utilised in tissue engineering. Int J Oral Sci, 2019, 11(2): 20.
4.	康弟, 李洪波. SIRT1、SIRT3、SIRT6和SIRT7調控肺纖維化機制的研究進展. 中國呼吸與危重監護雜志. 2024, 23(1): 64-68.
5.	Wang Q, Xie ZL, Wu Q, et al. Role of various imbalances centered on alveolar epithelial cell/fibroblast apoptosis imbalance in the pathogenesis of idiopathic pulmonary fibrosis. Chin Med J (Engl), 2021, 134(3): 261-274.
6.	Korfei M, Skwarna S, Henneke I, et al. Aberrant expression and activity of histone deacetylases in sporadic idiopathic pulmonary fibrosis. Thorax, 2015, 70(11): 1022-1032.
7.	Zhang X, Liu H, Hock T, et al. Histone deacetylase inhibition downregulates collagen 3a1 in fibrotic lung fibroblasts. Int J Mol Sci, 2013, 14(10): 19605-19617.
8.	Shi MQ, Xu Y, Fu X, et al. Advances in targeting histone deacetylase for treatment of solid tumors. J Hematol Oncol, 2024, 17(1): 37.
9.	Pu J, Liu T, Wang X, et al. Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: Mechanisms, therapeutic implications, and future perspectives. Exp Hematol Oncol, 2024, 13(1): 45.
10.	Curcio A, Rocca R, Alcaro S, et al. The histone deacetylase family: Structural features and application of combined computational methods. Pharmaceuticals, 2024, 17(5): 620.
11.	Asmamaw MD, He A, Zhang LR, et al. Histone deacetylase complexes: Structure, regulation and function. Biochim Biophys Acta Rev Cancer, 2024, 1879(5): 189150.
12.	Han H, Feng X, He T, et al. Discussion on structure classification and regulation function of histone deacetylase and their inhibitor. Chem Biol Drug Des, 2024, 103(1): e14366.
13.	Kim JY, Cho H, Yoo J, et al. Pathological role of HDAC8: Cancer and beyond. Cells, 2022, 11(19): 3160.
14.	De Ruijter AJ, Van Gennip AH, Caron HN, et al. Histone deacetylases (HDACs): Characterization of the classical HDAC family. Biochem J, 2003, 370: 737-749.
15.	Deng M, Yang S, Ji Y, et al. Overexpression of peptidase inhibitor 16 attenuates angiotensin II-induced cardiac fibrosis via regulating HDAC1 of cardiac fibroblasts. J Cell Mol Med, 2020, 24(9): 5249-5259.
16.	Nguy?n-Thanh T, Kim D, Lee S, et al. Inhibition of histone deacetylase 1 ameliorates renal tubulointerstitial fibrosis via modulation of inflammation and extracellular matrix gene transcription in mice. Int J Mol Med, 2018, 41(1): 95-106.
17.	Li M, Zheng Y, Yuan H, et al. Effects of dynamic changes in histone acetylation and deacetylase activity on pulmonary fibrosis. Int Immunopharmacol, 2017, 52: 272-280.
18.	Xiong R, Geng B, Jiang W, et al. Histone deacetylase 3 deletion in alveolar type 2 epithelial cells prevents bleomycin-induced pulmonary fibrosis. Clin Epigenetics, 2023, 15(1): 182.
19.	Yuan H, Jiao L, Yu N, et al. Histone deacetylase 3-mediated inhibition of microRNA-19a-3p facilitates the development of rheumatoid arthritis-associated interstitial lung disease. Front Physiol, 2020, 11: 549656.
20.	Kwon KD, Choi MJ, Park JM, et al. Silencing histone deacetylase 2 using small hairpin RNA induces regression of fibrotic plaque in a rat model of peyronie's disease. BJU Int, 2014, 114(6): 926-936.
21.	Rao SS, Zhang XY, Shi MJ, et al. Suberoylanilide hydroxamic acid attenuates paraquat-induced pulmonary fibrosis by preventing smad7 from deacetylation in rats. J Thorac Dis, 2016, 8(9): 2485-2494.
22.	Sanders YY, Hagood JS, Liu H, et al. Histone deacetylase inhibition promotes fibroblast apoptosis and ameliorates pulmonary fibrosis in mice. Eur Respir J, 2014, 43(5): 1448-1458.
23.	Davies ER, Haitchi HM, Thatcher TH, et al. Spiruchostatin a inhibits proliferation and differentiation of fibroblasts from patients with pulmonary fibrosis. Am J Respir Cell Mol Biol, 2012, 46(5): 687-694.
24.	Korfei M, Stelmaszek D, Mackenzie B, et al. Comparison of the antifibrotic effects of the pan-histone deacetylase-inhibitor panobinostat versus the IPF-drug pirfenidone in fibroblasts from patients with idiopathic pulmonary fibrosis. PLoS One, 2018, 13(11): e0207915.
25.	Liu D, Zhu H, Gong L, et al. Histone deacetylases promote er stress induced epithelial mesenchymal transition in human lung epithelial cells. Cell Physiol Biochem, 2018, 46(5): 1821-1834.
26.	Sun L, He X, Kong J, et al. Menstrual blood-derived stem cells exosomal mir-let-7 to ameliorate pulmonary fibrosis through inhibiting ferroptosis by Sp3/HDAC2/Nrf2 signaling pathway. Int Immunopharmacol, 2024, 126: 111316.
27.	Ota C, Yamada M, Fujino N, et al. Histone deacetylase inhibitor restores surfactant protein-C expression in alveolar-epithelial type II cells and attenuates bleomycin-induced pulmonary fibrosis in vivo. Exp Lung Res, 2015, 41(8): 422-434.
28.	Hu L, Yu Y, Huang H, et al. Epigenetic regulation of interleukin 6 by histone acetylation in macrophages and its role in paraquat-induced pulmonary fibrosis. Front Immunol, 2016, 7: 696.
29.	Jeong SH, Son ES, Lee YE, et al. Histone deacetylase 3 promotes alveolar epithelial-mesenchymal transition and fibroblast migration under hypoxic conditions. Exp Mol Med, 2022, 54(7): 922-931.
30.	Chen F, Gao Q, Zhang L, et al. Inhibiting HDAC3 (histone deacetylase 3) aberration and the resultant Nrf2 (nuclear factor erythroid-derived 2-related factor-2) repression mitigates pulmonary fibrosis. Hypertension, 2021, 78(2): e15-e25.
31.	Walker CJ, Batan D, Bishop CT, et al. Extracellular matrix stiffness controls cardiac valve myofibroblast activation through epigenetic remodeling. Bioeng Transl Med, 2022, 7(3): e10394.
32.	Jain N, Iyer KV, Kumar A, et al. Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility. Proc Natl Acad Sci U S A, 2013, 110(28): 11349-11354.
33.	Toscano-Marquez F, Romero Y, Espina-Ordo?ez M, et al. Absence of HDAC3 by matrix stiffness promotes chromatin remodeling and fibroblast activation in idiopathic pulmonary fibrosis. Cells, 2023, 12(7): 1020.
34.	Zheng Q, Lei Y, Hui S, et al. HDAC3 promotes pulmonary fibrosis by activating NOTCH1 and STAT1 signaling and up-regulating inflammasome components AIM2 and ASC. Cytokine, 2022, 153: 155842.
35.	Yu H, Liu S, Wang S, et al. The involvement of HDAC3 in the pathogenesis of lung injury and pulmonary fibrosis. Front Immunol, 2024, 15: 1392145.
36.	Ziesché E, Kettner-Buhrow D, Weber A, et al. The coactivator role of histone deacetylase 3 in IL-1-signaling involves deacetylation of p65 NF-κB. Nucleic Acids Res, 2013, 41(1): 90-109.
37.	Sun W, Zhang N, Liu B, et al. HDAC3 inhibitor RGFP966 ameliorated neuroinflammation in the cuprizone-induced demyelinating mouse model and LPS-stimulated BV2 cells by downregulating the P2X7R/STAT3/NF-κb65/NLRP3 activation. ACS Chem Neurosci, 2022, 13(17): 2579-2598.
38.	Li Y, Liu C, Wang G, et al. HDAC3 inhibitor (BRD3308) modulates microglial pyroptosis and neuroinflammation through PPARγ/NLRP3/GSDMD to improve neurological function after intraventricular hemorrhage in mice. Neuropharmacology, 2023, 237: 109633.
39.	Colunga Biancatelli RML, Solopov PA, Catravas JD. The inflammasome nlr family pyrin domain-containing protein 3 (NLRP3) as a novel therapeutic target for idiopathic pulmonary fibrosis. Am J Pathol, 2022, 192(6): 837-846.
40.	Lee CH, Choi Y, Cho H, et al. Histone deacetylase 8 inhibition alleviates cholestatic liver injury and fibrosis. Biochem Pharmacol, 2021, 183: 114312.
41.	Zhang Y, Zou J, Tolbert E, et al. Identification of histone deacetylase 8 as a novel therapeutic target for renal fibrosis. Faseb j, 2020, 34(6): 7295-7310.
42.	Saito S, Zhuang Y, Suzuki T, et al. HDAC8 inhibition ameliorates pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol, 2019, 316(1): L175-l186.
43.	Karolczak-Bayatti M, Sweeney M, Cheng J, et al. Acetylation of heat shock protein 20 (hsp20) regulates human myometrial activity. J Biol Chem, 2011, 286(39): 34346-34355.
44.	Li J, Chen S, Cleary RA, et al. Histone deacetylase 8 regulates cortactin deacetylation and contraction in smooth muscle tissues. Am J Physiol Cell Physiol, 2014, 307(3): C288-295.
45.	Yu WC, Yeh TY, Ye CH, et al. Discovery of hdac6, HDAC8, and 6/8 inhibitors and development of cell-based drug screening models for the treatment of TGF-β-induced idiopathic pulmonary fibrosis. J Med Chem, 2023, 66(15): 10528-10557.
46.	Conforti F, Davies ER, Calderwood CJ, et al. The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis. Oncotarget, 2017, 8(30): 48737-48754.
47.	Schrump DS, Fischette MR, Nguyen DM, et al. Clinical and molecular responses in lung cancer patients receiving romidepsin. Clin Cancer Res, 2008, 14(1): 188-198.
48.	Noguchi S, Eitoku M, Moriya S, et al. Regulation of gene expression by sodium valproate in epithelial-to-mesenchymal transition. Lung, 2015, 193(5): 691-700.
49.	Chen L, Alam A, Pac-Soo A, et al. Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial-mesenchymal transition inhibition in vitro and in vivo. Lab Invest, 2021, 101(9): 1166-1175.
50.	Kabel AM, Omar MS, Elmaaboud MAA. Amelioration of bleomycin-induced lung fibrosis in rats by valproic acid and butyrate: Role of nuclear factor kappa-b, proinflammatory cytokines and oxidative stress. Int Immunopharmacol, 2016, 39: 335-342.
51.	Barter MJ, Pybus L, Litherland GJ, et al. HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes. Matrix Biol, 2010, 29(7): 602-612.
52.	Kamio K, Azuma A, Usuki J, et al. XPLN is modulated by HDAC inhibitors and negatively regulates SPARC expression by targeting mTORC2 in human lung fibroblasts. Pulm Pharmacol Ther, 2017, 44: 61-69.

1. Koudstaal T, Funke-Chambour M, Kreuter M, et al. Pulmonary fibrosis: from pathogenesis to clinical decision-making. Trends Mol Med, 2023, 29(12): 1076-1087.
2. Ahmad S, Zhang XL, Ahmad A. Epigenetic regulation of pulmonary inflammation. Semin Cell Dev Biol, 2024, 154: 346-354.
3. Lawlor L, Yang XB. Harnessing the HDAC-histone deacetylase enzymes, inhibitors and how these can be utilised in tissue engineering. Int J Oral Sci, 2019, 11(2): 20.
4. 康弟, 李洪波. SIRT1、SIRT3、SIRT6和SIRT7調控肺纖維化機制的研究進展. 中國呼吸與危重監護雜志. 2024, 23(1): 64-68.
5. Wang Q, Xie ZL, Wu Q, et al. Role of various imbalances centered on alveolar epithelial cell/fibroblast apoptosis imbalance in the pathogenesis of idiopathic pulmonary fibrosis. Chin Med J (Engl), 2021, 134(3): 261-274.
6. Korfei M, Skwarna S, Henneke I, et al. Aberrant expression and activity of histone deacetylases in sporadic idiopathic pulmonary fibrosis. Thorax, 2015, 70(11): 1022-1032.
7. Zhang X, Liu H, Hock T, et al. Histone deacetylase inhibition downregulates collagen 3a1 in fibrotic lung fibroblasts. Int J Mol Sci, 2013, 14(10): 19605-19617.
8. Shi MQ, Xu Y, Fu X, et al. Advances in targeting histone deacetylase for treatment of solid tumors. J Hematol Oncol, 2024, 17(1): 37.
9. Pu J, Liu T, Wang X, et al. Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: Mechanisms, therapeutic implications, and future perspectives. Exp Hematol Oncol, 2024, 13(1): 45.
10. Curcio A, Rocca R, Alcaro S, et al. The histone deacetylase family: Structural features and application of combined computational methods. Pharmaceuticals, 2024, 17(5): 620.
11. Asmamaw MD, He A, Zhang LR, et al. Histone deacetylase complexes: Structure, regulation and function. Biochim Biophys Acta Rev Cancer, 2024, 1879(5): 189150.
12. Han H, Feng X, He T, et al. Discussion on structure classification and regulation function of histone deacetylase and their inhibitor. Chem Biol Drug Des, 2024, 103(1): e14366.
13. Kim JY, Cho H, Yoo J, et al. Pathological role of HDAC8: Cancer and beyond. Cells, 2022, 11(19): 3160.
14. De Ruijter AJ, Van Gennip AH, Caron HN, et al. Histone deacetylases (HDACs): Characterization of the classical HDAC family. Biochem J, 2003, 370: 737-749.
15. Deng M, Yang S, Ji Y, et al. Overexpression of peptidase inhibitor 16 attenuates angiotensin II-induced cardiac fibrosis via regulating HDAC1 of cardiac fibroblasts. J Cell Mol Med, 2020, 24(9): 5249-5259.
16. Nguy?n-Thanh T, Kim D, Lee S, et al. Inhibition of histone deacetylase 1 ameliorates renal tubulointerstitial fibrosis via modulation of inflammation and extracellular matrix gene transcription in mice. Int J Mol Med, 2018, 41(1): 95-106.
17. Li M, Zheng Y, Yuan H, et al. Effects of dynamic changes in histone acetylation and deacetylase activity on pulmonary fibrosis. Int Immunopharmacol, 2017, 52: 272-280.
18. Xiong R, Geng B, Jiang W, et al. Histone deacetylase 3 deletion in alveolar type 2 epithelial cells prevents bleomycin-induced pulmonary fibrosis. Clin Epigenetics, 2023, 15(1): 182.
19. Yuan H, Jiao L, Yu N, et al. Histone deacetylase 3-mediated inhibition of microRNA-19a-3p facilitates the development of rheumatoid arthritis-associated interstitial lung disease. Front Physiol, 2020, 11: 549656.
20. Kwon KD, Choi MJ, Park JM, et al. Silencing histone deacetylase 2 using small hairpin RNA induces regression of fibrotic plaque in a rat model of peyronie's disease. BJU Int, 2014, 114(6): 926-936.
21. Rao SS, Zhang XY, Shi MJ, et al. Suberoylanilide hydroxamic acid attenuates paraquat-induced pulmonary fibrosis by preventing smad7 from deacetylation in rats. J Thorac Dis, 2016, 8(9): 2485-2494.
22. Sanders YY, Hagood JS, Liu H, et al. Histone deacetylase inhibition promotes fibroblast apoptosis and ameliorates pulmonary fibrosis in mice. Eur Respir J, 2014, 43(5): 1448-1458.
23. Davies ER, Haitchi HM, Thatcher TH, et al. Spiruchostatin a inhibits proliferation and differentiation of fibroblasts from patients with pulmonary fibrosis. Am J Respir Cell Mol Biol, 2012, 46(5): 687-694.
24. Korfei M, Stelmaszek D, Mackenzie B, et al. Comparison of the antifibrotic effects of the pan-histone deacetylase-inhibitor panobinostat versus the IPF-drug pirfenidone in fibroblasts from patients with idiopathic pulmonary fibrosis. PLoS One, 2018, 13(11): e0207915.
25. Liu D, Zhu H, Gong L, et al. Histone deacetylases promote er stress induced epithelial mesenchymal transition in human lung epithelial cells. Cell Physiol Biochem, 2018, 46(5): 1821-1834.
26. Sun L, He X, Kong J, et al. Menstrual blood-derived stem cells exosomal mir-let-7 to ameliorate pulmonary fibrosis through inhibiting ferroptosis by Sp3/HDAC2/Nrf2 signaling pathway. Int Immunopharmacol, 2024, 126: 111316.
27. Ota C, Yamada M, Fujino N, et al. Histone deacetylase inhibitor restores surfactant protein-C expression in alveolar-epithelial type II cells and attenuates bleomycin-induced pulmonary fibrosis in vivo. Exp Lung Res, 2015, 41(8): 422-434.
28. Hu L, Yu Y, Huang H, et al. Epigenetic regulation of interleukin 6 by histone acetylation in macrophages and its role in paraquat-induced pulmonary fibrosis. Front Immunol, 2016, 7: 696.
29. Jeong SH, Son ES, Lee YE, et al. Histone deacetylase 3 promotes alveolar epithelial-mesenchymal transition and fibroblast migration under hypoxic conditions. Exp Mol Med, 2022, 54(7): 922-931.
30. Chen F, Gao Q, Zhang L, et al. Inhibiting HDAC3 (histone deacetylase 3) aberration and the resultant Nrf2 (nuclear factor erythroid-derived 2-related factor-2) repression mitigates pulmonary fibrosis. Hypertension, 2021, 78(2): e15-e25.
31. Walker CJ, Batan D, Bishop CT, et al. Extracellular matrix stiffness controls cardiac valve myofibroblast activation through epigenetic remodeling. Bioeng Transl Med, 2022, 7(3): e10394.
32. Jain N, Iyer KV, Kumar A, et al. Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility. Proc Natl Acad Sci U S A, 2013, 110(28): 11349-11354.
33. Toscano-Marquez F, Romero Y, Espina-Ordo?ez M, et al. Absence of HDAC3 by matrix stiffness promotes chromatin remodeling and fibroblast activation in idiopathic pulmonary fibrosis. Cells, 2023, 12(7): 1020.
34. Zheng Q, Lei Y, Hui S, et al. HDAC3 promotes pulmonary fibrosis by activating NOTCH1 and STAT1 signaling and up-regulating inflammasome components AIM2 and ASC. Cytokine, 2022, 153: 155842.
35. Yu H, Liu S, Wang S, et al. The involvement of HDAC3 in the pathogenesis of lung injury and pulmonary fibrosis. Front Immunol, 2024, 15: 1392145.
36. Ziesché E, Kettner-Buhrow D, Weber A, et al. The coactivator role of histone deacetylase 3 in IL-1-signaling involves deacetylation of p65 NF-κB. Nucleic Acids Res, 2013, 41(1): 90-109.
37. Sun W, Zhang N, Liu B, et al. HDAC3 inhibitor RGFP966 ameliorated neuroinflammation in the cuprizone-induced demyelinating mouse model and LPS-stimulated BV2 cells by downregulating the P2X7R/STAT3/NF-κb65/NLRP3 activation. ACS Chem Neurosci, 2022, 13(17): 2579-2598.
38. Li Y, Liu C, Wang G, et al. HDAC3 inhibitor (BRD3308) modulates microglial pyroptosis and neuroinflammation through PPARγ/NLRP3/GSDMD to improve neurological function after intraventricular hemorrhage in mice. Neuropharmacology, 2023, 237: 109633.
39. Colunga Biancatelli RML, Solopov PA, Catravas JD. The inflammasome nlr family pyrin domain-containing protein 3 (NLRP3) as a novel therapeutic target for idiopathic pulmonary fibrosis. Am J Pathol, 2022, 192(6): 837-846.
40. Lee CH, Choi Y, Cho H, et al. Histone deacetylase 8 inhibition alleviates cholestatic liver injury and fibrosis. Biochem Pharmacol, 2021, 183: 114312.
41. Zhang Y, Zou J, Tolbert E, et al. Identification of histone deacetylase 8 as a novel therapeutic target for renal fibrosis. Faseb j, 2020, 34(6): 7295-7310.
42. Saito S, Zhuang Y, Suzuki T, et al. HDAC8 inhibition ameliorates pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol, 2019, 316(1): L175-l186.
43. Karolczak-Bayatti M, Sweeney M, Cheng J, et al. Acetylation of heat shock protein 20 (hsp20) regulates human myometrial activity. J Biol Chem, 2011, 286(39): 34346-34355.
44. Li J, Chen S, Cleary RA, et al. Histone deacetylase 8 regulates cortactin deacetylation and contraction in smooth muscle tissues. Am J Physiol Cell Physiol, 2014, 307(3): C288-295.
45. Yu WC, Yeh TY, Ye CH, et al. Discovery of hdac6, HDAC8, and 6/8 inhibitors and development of cell-based drug screening models for the treatment of TGF-β-induced idiopathic pulmonary fibrosis. J Med Chem, 2023, 66(15): 10528-10557.
46. Conforti F, Davies ER, Calderwood CJ, et al. The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis. Oncotarget, 2017, 8(30): 48737-48754.
47. Schrump DS, Fischette MR, Nguyen DM, et al. Clinical and molecular responses in lung cancer patients receiving romidepsin. Clin Cancer Res, 2008, 14(1): 188-198.
48. Noguchi S, Eitoku M, Moriya S, et al. Regulation of gene expression by sodium valproate in epithelial-to-mesenchymal transition. Lung, 2015, 193(5): 691-700.
49. Chen L, Alam A, Pac-Soo A, et al. Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial-mesenchymal transition inhibition in vitro and in vivo. Lab Invest, 2021, 101(9): 1166-1175.
50. Kabel AM, Omar MS, Elmaaboud MAA. Amelioration of bleomycin-induced lung fibrosis in rats by valproic acid and butyrate: Role of nuclear factor kappa-b, proinflammatory cytokines and oxidative stress. Int Immunopharmacol, 2016, 39: 335-342.
51. Barter MJ, Pybus L, Litherland GJ, et al. HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes. Matrix Biol, 2010, 29(7): 602-612.
52. Kamio K, Azuma A, Usuki J, et al. XPLN is modulated by HDAC inhibitors and negatively regulates SPARC expression by targeting mTORC2 in human lung fibroblasts. Pulm Pharmacol Ther, 2017, 44: 61-69.

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Ⅰ類組蛋白去乙酰化酶在肺纖維化中的研究進展

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