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Research Article

TGF-β1-based CRISPR/Cas9 Gene Therapy Attenuates Radiation-induced Lung Injury

Author(s): Shuai Zhen*, Rong Qiang, Jiaojiao Lu, Xiaoqian Tuo, Xiling Yang and Xu Li

Volume 22, Issue 1, 2022

Published on: 30 December, 2020

Page: [59 - 65] Pages: 7

DOI: 10.2174/1566523220666201230100523

Price: $65

Abstract

Background: Radiation-induced lung injury (RILI) is lacking effective therapeutic strategies. In this study, we conducted TGF-β1-based CRISPR/Cas9 gene therapy for RILI.

Objective: Mouse lungs were irradiated with a single-dose of 20-Gy gamma rays followed by intravenous administration of Ad-CRISPR-TGF-β1 or Ad- CRISPR-Null.

Methods: Haematoxylin and eosin staining, as well as Masson staining, were performed to observe lung morphology. Albumin and IgM concentrations in bronchoalveolar lavage fluid were measured by ELISA. Cytokine levels were measured using ELISA and/or real-time PCR with terminal deoxynucleotidyl transferase-mediated nick-end labelling.

Results: Ad-CRISPR-TTGF-β1 improved histopathological and biochemical markers of lung injury, reduced secretion and expression of inflammatory cytokines, and inhibited progression of fibrosis. Importantly, the SK1/S1P axis, which is known to play a key role via S1P1 in TGF-β1-dependent S1PR pattern remodelling, is responsible for promoting fibrosis.

Conclusion: Our results indicate novel insights for RILI therapy.

Keywords: CRISPR/Cas9, fibrosis, inflammation, lung, gene therapy, CRISPR/Cas9.

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[1]
Zhang J, Li B, Ding X, et al. Genetic variants in inducible nitric oxide synthase gene are associated with the risk of radiation-induced lung injury in lung cancer patients receiving definitive thoracic radiation. Radiother Oncol 2014; 111(2): 194-8.
[http://dx.doi.org/10.1016/j.radonc.2014.03.001] [PMID: 24746566]
[2]
Zheng L, Zhu Q, Xu C, et al. Glycyrrhizin mitigates radiation-induced acute lung injury by inhibiting the HMGB1/TLR4 signalling pathway. J Cell Mol Med 2020; 24(1): 214-26.
[http://dx.doi.org/10.1111/jcmm.14703] [PMID: 31657123]
[3]
Zhou J, Wu P, Sun H, Zhou H, Zhang Y, Xiao Z. Lung tissue extracellular matrix-derived hydrogels protect against radiation-induced lung injury by suppressing epithelial-mesenchymal transition. J Cell Physiol 2020; 235(3): 2377-88.
[http://dx.doi.org/10.1002/jcp.29143] [PMID: 31490023]
[4]
Zhang C, Zeng W, Yao Y, et al. Naringenin Ameliorates Radiation-Induced Lung Injury by Lowering IL-1β Level. J Pharmacol Exp Ther 2018; 366(2): 341-8.
[http://dx.doi.org/10.1124/jpet.118.248807] [PMID: 29866791]
[5]
Zhang Y, Zhang X, Rabbani ZN, Jackson IL, Vujaskovic Z. Oxidative stress mediates radiation lung injury by inducing apoptosis. Int J Radiat Oncol Biol Phys 2012; 83(2): 740-8.
[http://dx.doi.org/10.1016/j.ijrobp.2011.08.005] [PMID: 22270165]
[6]
Zhang H, Jiang T, Yu H, et al. Polyene phosphatidylcholine protects against radiation induced tissue injury without affecting radiotherapeutic efficacy in lung cancer. Am J Cancer Res 2019; 9(6): 1091-103.
[PMID: 31285944]
[7]
Liu M, Han X, Liu H, Chen D, Li Y, Hu W. The effects of CRISPR-Cas9 knockout of the TGF-β1 gene on antler cartilage cells in vitro. Cell Mol Biol Lett 2019; 24: 44.
[http://dx.doi.org/10.1186/s11658-019-0171-z] [PMID: 31285745]
[8]
Zhang W, Wang J, Tang M, et al. Quantitative study of lung perfusion SPECT scanning and pulmonary function testing for early radiation-induced lung injury in patients with locally advanced non-small cell lung cancer. Exp Ther Med 2012; 3(4): 631-5.
[http://dx.doi.org/10.3892/etm.2012.468] [PMID: 22969942]
[9]
Zhou S, Nissao E, Jackson IL, et al. Radiation-induced lung injury is mitigated by blockade of gastrin-releasing peptide. Am J Pathol 2013; 182(4): 1248-54.
[http://dx.doi.org/10.1016/j.ajpath.2012.12.024] [PMID: 23395092]
[10]
Zhen S, Hua L, Takahashi Y, Narita S, Liu YH, Li Y. In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by CRISPR/Cas9. Biochem Biophys Res Commun 2014; 450(4): 1422-6.
[http://dx.doi.org/10.1016/j.bbrc.2014.07.014] [PMID: 25044113]
[11]
Kasper M, Schuh D, Müller M. Bauhinia purpurea lectin (BPA) binding of rat type I pneumocytes: alveolar epithelial alterations after radiation-induced lung injury. Exp Toxicol Pathol 1994; 46(4-5): 361-7.
[http://dx.doi.org/10.1016/S0940-2993(11)80118-1] [PMID: 7894248]
[12]
Wang L, Zhang J, Wang B, Wang G, Xu J. Blocking HMGB1 signal pathway protects early radiation-induced lung injury. Int J Clin Exp Pathol 2015; 8(5): 4815-22.
[PMID: 26191172]
[13]
Xu PT, Maidment BW III, Antonic V, et al. Cerium Oxide Nanoparticles: A Potential Medical Countermeasure to Mitigate Radiation-Induced Lung Injury in CBA/J Mice. Radiat Res 2016; 185(5): 516-26.
[http://dx.doi.org/10.1667/RR14261.1] [PMID: 27135969]
[14]
Xu S, Liu C, Ji HL. Concise review: Therapeutic potential of the mesenchymal stem cell derived secretome and extracellular vesicles for radiation-induced lung injury: Progress and hypotheses. Stem Cells Transl Med 2019; 8(4): 344-54.
[http://dx.doi.org/10.1002/sctm.18-0038] [PMID: 30618085]
[15]
Yin Z, Deng S, Liang Z, Wang Q. Consecutive CT-guided core needle tissue biopsy of lung lesions in the same dog at different phases of radiation-induced lung injury. J Radiat Res (Tokyo) 2016; 57(5): 499-504.
[http://dx.doi.org/10.1093/jrr/rrw053] [PMID: 27422930]
[16]
Wang H, Yang YF, Zhao L, et al. Hepatocyte growth factor gene-modified mesenchymal stem cells reduce radiation-induced lung injury. Hum Gene Ther 2013; 24(3): 343-53.
[http://dx.doi.org/10.1089/hum.2012.177] [PMID: 23458413]
[17]
Susskind H, Weber DA, Lau YH, et al. Impaired permeability in radiation-induced lung injury detected by technetium-99m-DTPA lung clearance. J Nucl Med 1997; 38(6): 966-71.
[PMID: 9189152]
[18]
Xie L, Zhou J, Zhang S, et al. Integrating microRNA and mRNA expression profiles in response to radiation-induced injury in rat lung. Radiat Oncol 2014; 9: 111.
[http://dx.doi.org/10.1186/1748-717X-9-111] [PMID: 24886372]
[19]
Xia P, Cao K, Hu X, et al. KATP channel blocker glibenclamide prevents radiation-induced lung injury and inhibits radiation-induced apoptosis of vascular endothelial cells by increased Ca2+ influx and subsequent PKC activation. Radiat Res 2020; 193(2): 171-85.
[http://dx.doi.org/10.1667/RR15381.1] [PMID: 31877256]
[20]
Kong FM, Anscher MS, Sporn TA, et al. Loss of heterozygosity at the mannose 6-phosphate insulin-like growth factor 2 receptor (M6P/IGF2R) locus predisposes patients to radiation-induced lung injury. Int J Radiat Oncol Biol Phys 2001; 49(1): 35-41.
[http://dx.doi.org/10.1016/S0360-3016(00)01377-8] [PMID: 11163495]
[21]
Yang K, Palm J, König J, et al. Matrix-Metallo-Proteinases and their tissue inhibitors in radiation-induced lung injury. Int J Radiat Biol 2007; 83(10): 665-76.
[http://dx.doi.org/10.1080/09553000701558977] [PMID: 17729161]
[22]
Wu X, Ji H, Wang Y, et al. Melatonin alleviates radiation-induced lung injury via regulation of miR-30e/NLRP3 axis. Oxid Med Cell Longev 2019; 20194087298
[http://dx.doi.org/10.1155/2019/4087298] [PMID: 30755784]
[23]
Yamamoto N, Miyamoto T, Nishimura H, et al. Preoperative carbon ion radiotherapy for non-small cell lung cancer with chest wall invasion--pathological findings concerning tumor response and radiation induced lung injury in the resected organs. Lung Cancer 2003; 42(1): 87-95.
[http://dx.doi.org/10.1016/S0169-5002(03)00243-5] [PMID: 14512192]
[24]
Wang J, Zhang YY, Cheng J, Zhang JL, Li BS. Preventive and therapeutic effects of quercetin on experimental radiation induced lung injury in mice. Asian Pac J Cancer Prev 2015; 16(7): 2909-14.
[http://dx.doi.org/10.7314/APJCP.2015.16.7.2909] [PMID: 25854382]
[25]
Zhang K, Yang S, Zhu Y, Mo A, Zhang D, Liu L. Protection against acute radiation-induced lung injury: a novel role for the anti-angiogenic agent Endostar. Mol Med Rep 2012; 6(2): 309-15.
[http://dx.doi.org/10.3892/mmr.2012.903] [PMID: 22562140]
[26]
Yildiz OG, Soyuer S, Saraymen R, Eroglu C. Protective effects of caffeic acid phenethyl ester on radiation induced lung injury in rats. Clin Invest Med 2008; 31(5): E242-7.
[http://dx.doi.org/10.25011/cim.v31i5.4870] [PMID: 18980713]

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