Effect of mTOR Signaling Pathway Inhibition on Bleomycin-induced Pulmonary Fibrosis

Egao YIN; Wen LEI; Mei YANG; Yongjun LIU; Zhaoxing DONG

doi:10.12259/j.issn.2095-610X.S20250608

Volume 46 Issue 6

Jun. 2025

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Article Navigation > Journal of Kunming Medical University > 2025 > 46(6): 64-70

Egao YIN, Wen LEI, Mei YANG, Yongjun LIU, Zhaoxing DONG. Effect of mTOR Signaling Pathway Inhibition on Bleomycin-induced Pulmonary Fibrosis[J]. Journal of Kunming Medical University, 2025, 46(6): 64-70. doi: 10.12259/j.issn.2095-610X.S20250608

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Egao YIN, Wen LEI, Mei YANG, Yongjun LIU, Zhaoxing DONG. Effect of mTOR Signaling Pathway Inhibition on Bleomycin-induced Pulmonary Fibrosis[J]. Journal of Kunming Medical University, 2025, 46(6): 64-70. doi: 10.12259/j.issn.2095-610X.S20250608

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Effect of mTOR Signaling Pathway Inhibition on Bleomycin-induced Pulmonary Fibrosis

doi: 10.12259/j.issn.2095-610X.S20250608

Egao YIN^{1, 2},
Wen LEI²,
Mei YANG³,
Yongjun LIU⁴,
Zhaoxing DONG^{5
,
,}

1.
Respiratory Medicine，Aba Tibetan and Qiang Autonomous Prefecture People’s Hospital，Aba Sichuan 623200
2.
Respiratory and Critical Medicine Department，The Second Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650101
3.
Respiratory and Critical Medicine Department，Affiliated Hospital of Yunnan University，Kunming Yunnan 650101
4.
Yunnan Normal University Hospital，Kunming Yunnan 650101
5.
Respiratory and Critical Care Medicine Department of the Second Hospital of Ningbo，Ningbo Zhejiang 315000，China

Received Date: 2024-05-25
Publish Date: 2025-06-25

Abstract

Abstract

Objective To investigate the effect of mTOR signaling pathway on bleomycin-induced pulmonary fibrosis. Methods 30 healthy male C57BL/6 mice aged 6～8 weeks were fed for 1 week and divided into control group （NC group, n = 5）, bleomycin group （BLM group, n = 5）, and rapamycin + bleomycin group （Rapa+BLM group, n = 5）. Mice were euthanized by cervical dislocation at 7 and 28 days, and lung tissues were collected. HE staining was used to observe inflammatory infiltration in lung tissue, and Masson's staining was used to assess the severity of lung fibrosis. Western blot and qPCR were used to detect the expression levels of collagen I, collagen III and α-SMA to evaluate the degree of lung fibrosis. Western blot was used to detect the expression of mTOR, P70S6K and their phosphorylation levels in each group. Results Compared with the NC group, the BLM group showed thickened alveolar septa, obvious inflammatory changes, and collagen deposition.The protein expression of Collagen I, Collagen III, and α-SMA were significantly increased （P < 0.01）, with increased mRNA expression of Collagen I, Collagen III, and α-SMA （P < 0.05）, and elevated p-mTOR and p-p70S6K expression （P < 0.05）. Compared with the BLM group, the Rapa+BLM group showed improved lung tissue structure, reduced inflammation and collagen deposition, a downward trend in Collagen I, Collagen III, and α-SMA protein expression （P > 0.05）, a downward trend in Collagen I mRNA （P > 0.05）, and decreased Collagen III and α-SMA mRNA expression （P < 0.05）. Conclusion Abnormal mTOR activation was observed in bleomycin-induced pulmonary fibrosis; inhibiting mTOR signaling pathway activation can effectively alleviate the formation of pulmonary fibrosis.
- Pulmonary fibrosis,
- Bleomycin,
- Rapamycin

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References(21)

References

[1]	Aggarwal K,Arora S,Nagpal K. Pulmonary fibrosis: Unveiling the pathogenesis,exploring therapeutic targets,and advancements in drug delivery strategies[J]. AAPS PharmSciTech,2023,24(6):152. doi: 10.1208/s12249-023-02618-4
[2]	De Lena M,Guzzon A,Monfardini S,et al. Clinical,radiologic,and histopathologic studies on pulmonary toxicity induced by treatment with bleomycin (NSC-125066)[J]. Cancer Chemother Rep,1972,56(3):343-356.
[3]	Adamson I Y,Bowden D H. The pathogenesis of bleomycin-induced pulmonary fibrosis in mice[J]. Am J Pathol,1974,77(2):185-197.
[4]	Snider G L,Celli B R,Goldstein R et al. Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin. Lung volumes,volume-pressure relations,carbon monoxide uptake,and arterial blood gas studied[J]. Am Rev Respir Dis,1978,117(2):289-297.
[5]	Goldstein R,Lucey E,Franzblau C,et al. Failure of mechanical properties to parallel changes in lung connective tissue composition in bleomycin-induced pulmonary fibrosis in hamsters[J]. Am Rev Respir Dis,1979,120(1):67-73.
[6]	Koudstaal T,Funke-Chambour M,Kreuter M,et al. Pulmonary fibrosis: From pathogenesis to clinical decision-making[J]. Trends Mol Med,2023,29(12):1076-1087. doi: 10.1016/j.molmed.2023.08.010
[7]	林艺凯,马爱平,周伟跃,等. mTOR信号通路在博来霉素诱导小鼠肺纤维化中的作用机制研究[J]. 中国呼吸与危重监护杂志,2018,17(2):178-182.
[8]	邓艳,赵红玉,朱丽萍,等. 硫酸羟氯喹通过PI3K/AKt/mTOR信号通路对百草枯致小鼠肺纤维化影响[J]. 中国呼吸与危重监护杂志,2024,23(3):192-199.
[9]	Cong L H,Li T,Wang H,et al. IL-17A-producing T cells exacerbate fine particulate matter-induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR-mediated autophagy[J]. J Cell Mol Med,2020,24(15):8532-8544. doi: 10.1111/jcmm.15475
[10]	Liu Y,Zhong W,Zhang J,et al. Tetrandrine Modulates Rheb-mTOR signaling-mediated selective autophagy and protects pulmonary fibrosis[J]. Front Pharmacol,2021,11(12):739220.
[11]	Pan L,Cheng Y,Yang W,et al. Nintedanib ameliorates bleomycin-induced pulmonary fibrosis,inflammation,apoptosis,and oxidative stress by modulating PI3K/Akt/mTOR pathway in mice[J]. Inflammation,2023,46(4):1531-1542. doi: 10.1007/s10753-023-01825-2
[12]	Fei Q,Zhong D L,Wen D H,et al. LncRNA TUG1 promotes pulmonary fibrosis progression via up-regulating CDC27 and activating PI3K/Akt/mTOR pathway[J]. Epigenetics,2023,18(1):2195305. doi: 10.1080/15592294.2023.2195305
[13]	Han Q,Lin L,Zhao B,et al. Inhibition of mTOR ameliorates bleomycin-induced pulmonary fibrosis by regulating epithelial-mesenchymal transition[J]. Biochem Biophys Res Commun,2018,500(4):839-845. doi: 10.1016/j.bbrc.2018.04.148
[14]	Molina-Molina M,Machahua-Huamani C,Vicens-Zygmunt V,et al. Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells[J]. BMC Pulm Med,2018,18(1):63. doi: 10.1186/s12890-018-0626-4
[15]	Gui Y S,Wang L,Tian X,et al. mTOR overactivation and compromised autophagy in the pathogenesis of pulmonary fibrosis[J]. PLoS One,2015,10(9):e0138625. doi: 10.1371/journal.pone.0138625
[16]	Helal M G,Said E. Carvedilol attenuates experimentally induced silicosis in rats via modulation of P-AKT/mTOR/TGFβ1 signaling[J]. Int Immunopharmacol,2019,70:47-55. doi: 10.1016/j.intimp.2019.02.011
[17]	Woodcock H V,Eley J D,Guillotin D,et al. The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis[J]. Nat Commun,2019,10(1):6. doi: 10.1038/s41467-018-07858-8
[18]	Platé M,Guillotin D,Chambers R C. The promise of mTOR as a therapeutic target pathway in idiopathic pulmonary fibrosis[J]. Eur Respir Rev,2020,29(157):200269. doi: 10.1183/16000617.0269-2020
[19]	马爱平,李久荣,索文昊,等. mTOR抑制剂对博来霉素诱导小鼠肺纤维化的作用研究[J]. 中国卫生标准管理,2019,10(6):108-111.
[20]	Buschhausen L,Kamm M,Arns W,et al. Successful treatment of a severe case of idiopathic pulmonary fibrosis with rapamycin[J]. Med Klin (Munich),2005,100(3):161-164. doi: 10.1007/s00063-005-1015-3
[21]	Drion C M,Borm L E,Kooijman L,et al. Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats[J]. Epilepsia,2016,57(5):688-697. doi: 10.1111/epi.13345

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