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肺靶向性肌浆网Ca2+-ATP酶2a基因治疗:从发现到在博来霉素诱导的肺纤维化中的治疗应用

Lung-targeted SERCA2a Gene Therapy: From Discovery to Therapeutic Application in Bleomycin-Induced Pulmonary Fibrosis.

作者信息

Bisserier Malik, Hadri Lahouaria

机构信息

Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

出版信息

J Cell Immunol. 2020;2(4):149-156. Epub 2020 May 6.

PMID:32587955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7316402/
Abstract

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by an accumulation of scar tissue within the lungs and the common presence of usual interstitial pneumonia. Unfortunately, only a few FDA-approved therapeutic options are currently available for the treatment of IPF and IPF remains associated with poor prognosis. Therefore, the identification of new pharmacological targets and strategies are critical for the treatment of IPF. This commentary aims to further discuss the role of sarcoplasmic reticulum Ca-ATPase 2a and its downstream signaling in IPF. Finally, this commentary offers new insights and perspectives regarding the therapeutic potential of AAV-mediated SERCA2A gene therapy as an emerging therapy for respiratory diseases.

摘要

特发性肺纤维化(IPF)是一种间质性肺疾病,其特征是肺部瘢痕组织积聚以及普通型间质性肺炎普遍存在。不幸的是,目前FDA批准的用于治疗IPF的治疗选择很少,且IPF的预后仍然很差。因此,确定新的药理学靶点和策略对于IPF的治疗至关重要。本评论旨在进一步探讨肌浆网Ca-ATP酶2a及其下游信号在IPF中的作用。最后,本评论就腺相关病毒介导的SERCA2A基因治疗作为一种新兴的呼吸系统疾病治疗方法的治疗潜力提供了新的见解和观点。

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J Cell Immunol. 2020;2(4):149-156. Epub 2020 May 6.
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Combination Therapy with STAT3 Inhibitor Enhances SERCA2a-Induced BMPR2 Expression and Inhibits Pulmonary Arterial Hypertension.联合使用 STAT3 抑制剂增强 SERCA2a 诱导的 BMPR2 表达并抑制肺动脉高压。
Int J Mol Sci. 2021 Aug 24;22(17):9105. doi: 10.3390/ijms22179105.
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引用本文的文献

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Progress in Respiratory Gene Therapy.呼吸系统基因治疗的进展。
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2
Novel Insights into the Therapeutic Potential of Lung-Targeted Gene Transfer in the Most Common Respiratory Diseases.新型见解:肺部靶向基因转移在最常见呼吸系统疾病中的治疗潜力。
Cells. 2022 Mar 12;11(6):984. doi: 10.3390/cells11060984.
3
Combination Therapy with STAT3 Inhibitor Enhances SERCA2a-Induced BMPR2 Expression and Inhibits Pulmonary Arterial Hypertension.联合使用 STAT3 抑制剂增强 SERCA2a 诱导的 BMPR2 表达并抑制肺动脉高压。

本文引用的文献

1
Del-1, an Endogenous Inhibitor of TGF-β Activation, Attenuates Fibrosis.Del-1,一种内源性 TGF-β 激活抑制剂,可减轻纤维化。
Front Immunol. 2020 Feb 7;11:68. doi: 10.3389/fimmu.2020.00068. eCollection 2020.
2
The deubiquitinase OTUB1 augments NF-κB-dependent immune responses in dendritic cells in infection and inflammation by stabilizing UBC13.去泛素化酶 OTUB1 通过稳定 UBC13 增强感染和炎症中树突状细胞内 NF-κB 依赖性免疫应答。
Cell Mol Immunol. 2021 Jun;18(6):1512-1527. doi: 10.1038/s41423-020-0362-6. Epub 2020 Feb 5.
3
AAV1.SERCA2a Gene Therapy Reverses Pulmonary Fibrosis by Blocking the STAT3/FOXM1 Pathway and Promoting the SNON/SKI Axis.
Int J Mol Sci. 2021 Aug 24;22(17):9105. doi: 10.3390/ijms22179105.
AAV1.SERCA2a 基因治疗通过阻断 STAT3/FOXM1 通路和促进 SNON/SKI 轴逆转肺纤维化。
Mol Ther. 2020 Feb 5;28(2):394-410. doi: 10.1016/j.ymthe.2019.11.027. Epub 2019 Dec 6.
4
Antifibrotic therapy for idiopathic pulmonary fibrosis: time to treat.特发性肺纤维化的抗纤维化治疗:是时候治疗了。
Respir Res. 2019 Sep 6;20(1):205. doi: 10.1186/s12931-019-1161-4.
5
Intra-tracheal gene delivery of aerosolized SERCA2a to the lung suppresses ventricular arrhythmias in a model of pulmonary arterial hypertension.经气管内气道输送 SERCA2a 基因到肺部可抑制肺动脉高压模型中的室性心律失常。
J Mol Cell Cardiol. 2019 Feb;127:20-30. doi: 10.1016/j.yjmcc.2018.11.017. Epub 2018 Nov 28.
6
Idiopathic Pulmonary Fibrosis: Epidemiology, Natural History, Phenotypes.特发性肺纤维化:流行病学、自然史、表型
Med Sci (Basel). 2018 Nov 29;6(4):110. doi: 10.3390/medsci6040110.
7
Safety and long-term efficacy of AAV1.SERCA2a using nebulizer delivery in a pig model of pulmonary hypertension.在肺动脉高压猪模型中使用雾化器递送AAV1.SERCA2a的安全性和长期疗效。
Pulm Circ. 2018 Oct-Dec;8(4):2045894018799738. doi: 10.1177/2045894018799738. Epub 2018 Aug 21.
8
Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease.转录共激活因子 Ski 和 SnoN 是 TGF-β/Smad 信号通路在健康和疾病中的主要调节因子。
Signal Transduct Target Ther. 2018 Jun 8;3:15. doi: 10.1038/s41392-018-0015-8. eCollection 2018.
9
FOXM1 is a critical driver of lung fibroblast activation and fibrogenesis.FOXM1 是肺成纤维细胞激活和纤维化的关键驱动因子。
J Clin Invest. 2018 Jun 1;128(6):2389-2405. doi: 10.1172/JCI87631. Epub 2018 May 7.
10
Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis.探索类似特发性肺纤维化的动物模型。
Front Med (Lausanne). 2017 Jul 28;4:118. doi: 10.3389/fmed.2017.00118. eCollection 2017.