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博来霉素 A5 抑制 Drp1 介导的线粒体分裂并诱导人鼻息肉衍生成纤维细胞凋亡。

Bleomycin A5 suppresses Drp1‑mediated mitochondrial fission and induces apoptosis in human nasal polyp‑derived fibroblasts.

机构信息

Department of Otorhinolaryngology‑Head and Neck Surgery, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510000, P.R. China.

出版信息

Int J Mol Med. 2021 Jan;47(1):346-360. doi: 10.3892/ijmm.2020.4797. Epub 2020 Nov 23.

DOI:10.3892/ijmm.2020.4797
PMID:33236140
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7723402/
Abstract

Intralesional injection of bleomycin‑A5 (BLE‑A5) is a novel treatment for nasal polyps. Our previous study clarified that BLE‑A5 could induce nasal polyp‑derived fibroblast (NPDF) apoptosis in nasal polyps. However, the detailed mechanisms are still unclear. The present study aimed to determine the effects of BLE‑A5 on NPDF mitochondrial dynamics and provide a theoretical basis for the local application of BLE‑A5 to treat nasal polyps. In the present study, an in vitro nasal polyp tissue culture model was used to define the BLE‑A5 target cell type in nasal polyps. NPDF primary cell culture was used to study the effects of BLE‑A5 on the mitochondrial dynamic‑related mechanism. The results showed that BLE‑A5 treatment of NPDFs caused mitochondrial‑mediated apoptosis. Dynamin‑related protein 1 (Drp1) was shown to be altered in BLE‑A5‑treated NPDFs. Drp1 knockdown increased the sensitivity of NPDFs to BLE‑A5 and exacerbated mitochondrial dysfunction. BLE‑A5 decreased cyclin B1‑CDK1 complex‑mediated phosphorylation of Drp1 and inhibited Drp1‑mediated mitophagy in NPDFs. Overall, the present study concluded that BLE‑A5 mainly induces NPDF apoptosis in nasal polyps. BLE‑A5 regulates the mitochondria by inhibiting Drp1 activation, resulting in NPDF mitochondrial dynamic disorder and apoptosis.

摘要

博来霉素 A5（BLE-A5）瘤内注射是一种治疗鼻息肉的新方法。我们之前的研究表明，BLE-A5 可以诱导鼻息肉衍生成纤维细胞（NPDF）在鼻息肉中发生凋亡。然而，其详细的机制尚不清楚。本研究旨在确定 BLE-A5 对 NPDF 线粒体动力学的影响，为 BLE-A5 局部应用于治疗鼻息肉提供理论依据。在本研究中，使用体外鼻息肉组织培养模型来确定鼻息肉中 BLE-A5 的靶细胞类型。使用 NPDF 原代细胞培养来研究 BLE-A5 对线粒体动力学相关机制的影响。结果表明，BLE-A5 处理 NPDF 可引起线粒体介导的细胞凋亡。在 BLE-A5 处理的 NPDF 中，动力相关蛋白 1（Drp1）发生改变。Drp1 敲低增加了 NPDF 对 BLE-A5 的敏感性，并加剧了线粒体功能障碍。BLE-A5 降低了 cyclin B1-CDK1 复合物介导的 Drp1 磷酸化，并抑制了 NPDF 中的 Drp1 介导的线粒体自噬。总之，本研究得出结论，BLE-A5 主要诱导鼻息肉中的 NPDF 发生凋亡。BLE-A5 通过抑制 Drp1 的激活来调节线粒体，导致 NPDF 线粒体动力学紊乱和凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/8165b09050c7/IJMM-47-01-0346-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/95539e51b256/IJMM-47-01-0346-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/7aa89ffaa5da/IJMM-47-01-0346-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/eada7a2423f3/IJMM-47-01-0346-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/07ff83fb4853/IJMM-47-01-0346-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/af28a371ad9e/IJMM-47-01-0346-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/bbdd10d5b576/IJMM-47-01-0346-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/b8c798944b74/IJMM-47-01-0346-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/8165b09050c7/IJMM-47-01-0346-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/95539e51b256/IJMM-47-01-0346-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/7aa89ffaa5da/IJMM-47-01-0346-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/eada7a2423f3/IJMM-47-01-0346-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/07ff83fb4853/IJMM-47-01-0346-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/af28a371ad9e/IJMM-47-01-0346-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/bbdd10d5b576/IJMM-47-01-0346-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/b8c798944b74/IJMM-47-01-0346-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9667/7723402/8165b09050c7/IJMM-47-01-0346-g07.jpg

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