• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

纤维瘤素杂合不足导致胸膜间皮细胞的细胞功能障碍。

Folliculin haploinsufficiency causes cellular dysfunction of pleural mesothelial cells.

机构信息

Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan.

The Study Group for Pneumothorax and Cystic Lung Diseases, Tokyo, 158-0095, Japan.

出版信息

Sci Rep. 2021 May 24;11(1):10814. doi: 10.1038/s41598-021-90184-9.

DOI:10.1038/s41598-021-90184-9
PMID:34031471
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8144428/
Abstract

Birt-Hogg-Dubé syndrome (BHDS), an autosomal dominant inheritance disease caused by folliculin (FLCN) mutations, is associated with lung cysts and spontaneous pneumothorax. The possibility of FLCN haploinsufficiency in pleural mesothelial cells (PMCs) contributing to development of pneumothorax has not yet been clarified. Electron microscopy revealed exposed intercellular boundaries between PMCs on visceral pleura and decreased electron density around the adherens junctions in BHDS. To characterize cellular function of PMCs in BHDS patients (BHDS-PMCs), during surgery for pneumothorax, we established the flow cytometry-based methods of isolating high-purity PMCs from pleural lavage fluid. BHDS-PMCs showed impaired cell attachment and a significant decrease in proliferation and migration, but a significant increase in apoptosis compared with PMCs from primary spontaneous pneumothorax (PSP) patients (PSP-PMCs). Microarray analysis using isolated PMCs revealed a significant alteration in the expression of genes belonging to Gene Ontology terms "cell-cell adhesion junction" and "cell adhesion molecule binding". Gene set enrichment analysis demonstrated that CDH1, encoding E-cadherin, was identified in the down-regulated leading edge of a plot in BHDS-PMCs. AMPK and LKB1 activation were significantly impaired in BHDS-PMCs compared with PSP-PMCs. Our findings indicate that FLCN haploinsufficiency may affect the E-cadherin-LKB1-AMPK axis and lead to abnormal cellular function in BHDS-PMCs.

摘要

Birt-Hogg-Dubé 综合征（BHDS）是一种常染色体显性遗传疾病，由滤泡素（FLCN）突变引起，与肺囊肿和自发性气胸有关。FLCN 部分功能不足是否会导致胸膜间皮细胞（PMCs）异常，从而导致气胸的发生，目前尚不清楚。电子显微镜显示 BHDS 的脏层胸膜 PMCs 细胞间边界暴露，黏着连接周围的电子密度降低。为了研究 BHDS 患者（BHDS-PMCs）的 PMCs 细胞功能，我们在气胸手术期间，建立了基于流式细胞术从胸腔灌洗液中分离高纯度 PMCs 的方法。与原发性自发性气胸（PSP）患者（PSP-PMCs）相比，BHDS-PMCs 的细胞黏附能力受损，增殖和迁移能力显著降低，而凋亡率显著增加。对分离的 PMCs 进行的微阵列分析显示，属于“细胞-细胞黏附连接”和“细胞黏附分子结合”GO 术语的基因表达发生显著改变。基因集富集分析表明，编码 E-钙黏蛋白的 CDH1 在 BHDS-PMCs 中下调，位于图的前沿。与 PSP-PMCs 相比，BHDS-PMCs 中的 AMPK 和 LKB1 激活明显受损。我们的研究结果表明，FLCN 部分功能不足可能会影响 E-钙黏蛋白-LKB1-AMPK 轴，导致 BHDS-PMCs 出现异常的细胞功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/1c9a1086ec31/41598_2021_90184_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/9548c38a8cf9/41598_2021_90184_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/545a411f2ea3/41598_2021_90184_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/1d27915891b5/41598_2021_90184_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/def933a68c32/41598_2021_90184_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/7a0c401546e1/41598_2021_90184_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/1c9a1086ec31/41598_2021_90184_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/9548c38a8cf9/41598_2021_90184_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/545a411f2ea3/41598_2021_90184_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/1d27915891b5/41598_2021_90184_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/def933a68c32/41598_2021_90184_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/7a0c401546e1/41598_2021_90184_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c7/8144428/1c9a1086ec31/41598_2021_90184_Fig6_HTML.jpg

相似文献

1
Folliculin haploinsufficiency causes cellular dysfunction of pleural mesothelial cells.纤维瘤素杂合不足导致胸膜间皮细胞的细胞功能障碍。
Sci Rep. 2021 May 24;11(1):10814. doi: 10.1038/s41598-021-90184-9.
2
Haploinsufficiency of the folliculin gene leads to impaired functions of lung fibroblasts in patients with Birt-Hogg-Dubé syndrome.卵泡抑素基因单倍剂量不足导致Birt-Hogg-Dubé综合征患者肺成纤维细胞功能受损。
Physiol Rep. 2016 Nov;4(21). doi: 10.14814/phy2.13025. Epub 2016 Nov 15.
3
FLCN-regulated miRNAs suppressed reparative response in cells and pulmonary lesions of Birt-Hogg-Dubé syndrome.FLCN 调控的 microRNA 抑制了 Birt-Hogg-Dubé 综合征细胞和肺部病变中的修复反应。
Thorax. 2020 Jun;75(6):476-485. doi: 10.1136/thoraxjnl-2019-213225. Epub 2020 Mar 17.
4
The Relevance of Family History Taking in the Detection and Management of Birt-Hogg-Dubé Syndrome.家族史采集在 Birt-Hogg-Dubé 综合征的检测和管理中的相关性。
Respiration. 2019;98(2):125-132. doi: 10.1159/000498973. Epub 2019 Jul 2.
5
Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression.Birt-Hogg-Dubé 肾肿瘤在遗传学上与其他肾肿瘤不同，并且与线粒体基因表达的上调有关。
BMC Med Genomics. 2010 Dec 16;3:59. doi: 10.1186/1755-8794-3-59.
6
Skin lesions of Birt-Hogg-Dubé syndrome: Clinical and histopathological findings in 31 Japanese patients who presented with pneumothorax and/or multiple lung cysts.Birt-Hogg-Dubé 综合征的皮肤损害：31 例以气胸和/或多发性肺囊肿为表现的日本患者的临床和组织病理学发现。
J Dermatol Sci. 2018 Jan;89(1):77-84. doi: 10.1016/j.jdermsci.2017.10.014. Epub 2017 Nov 2.
7
Birt-Hogg-Dube Syndrome with a Novel Mutation in the FLCN Gene.伴有卵泡抑素相关蛋白（FLCN）基因新突变的Birt-Hogg-Dube综合征
Genet Test Mol Biomarkers. 2017 Oct;21(10):632-634. doi: 10.1089/gtmb.2017.0070. Epub 2017 Aug 14.
8
Genotypic characteristics of Chinese patients with BHD syndrome and functional analysis of FLCN variants.BHD 综合征中国患者的基因特征及 FLCN 变异体的功能分析。
Orphanet J Rare Dis. 2019 Oct 15;14(1):223. doi: 10.1186/s13023-019-1198-y.
9
A case of Birt-Hogg-Dubé syndrome implying reduced or no wild-type folliculin without mutated protein is pathogenic.一例Birt-Hogg-Dubé综合征，提示野生型卵泡抑素减少或缺失且无突变蛋白，具有致病性。
Eur J Med Genet. 2020 Apr;63(4):103820. doi: 10.1016/j.ejmg.2019.103820. Epub 2019 Nov 25.
10
Identification of intragenic deletions and duplication in the FLCN gene in Birt-Hogg-Dubé syndrome.鉴定 Birt-Hogg-Dubé 综合征中 FLCN 基因的内含子缺失和重复。
Genes Chromosomes Cancer. 2011 Jun;50(6):466-77. doi: 10.1002/gcc.20872. Epub 2011 Mar 15.

引用本文的文献

1
Thyroid Carcinoma in Birt-Hogg-Dubé Syndrome: Case Series and Review of Literature.Birt-Hogg-Dubé综合征中的甲状腺癌：病例系列及文献综述
Thyroid. 2025 Jul;35(7):828-835. doi: 10.1089/thy.2024.0641. Epub 2025 Jun 5.
2
Clinical and genetic features of 334 Asian patients with Birt-Hogg-Dubé syndrome (BHDS) who presented with pulmonary cysts with or without a history of pneumothorax, with special reference to BHDS-associated pneumothorax.334 例亚洲人 Birt-Hogg-Dubé 综合征（BHDS）患者的临床和遗传特征，这些患者均表现为肺囊肿，无论是否有气胸病史，特别关注 BHDS 相关气胸。
PLoS One. 2023 Jul 25;18(7):e0289175. doi: 10.1371/journal.pone.0289175. eCollection 2023.
3

本文引用的文献

1
Normal mesothelial cell lines newly derived from human pleural biopsy explants.新从人胸膜活检外植体中分离得到的正常间皮细胞系。
Am J Physiol Lung Cell Mol Physiol. 2020 Oct 1;319(4):L652-L660. doi: 10.1152/ajplung.00141.2020. Epub 2020 Jul 29.
2
Nutrient Signaling and Lysosome Positioning Crosstalk Through a Multifunctional Protein, Folliculin.营养信号与溶酶体定位通过多功能蛋白卵泡抑素相互作用。
Front Cell Dev Biol. 2020 Mar 3;8:108. doi: 10.3389/fcell.2020.00108. eCollection 2020.
3
AMPK Activation Promotes Tight Junction Assembly in Intestinal Epithelial Caco-2 Cells.
Novel 3D organotypic co-culture model of pleura.
新型胸膜 3D 器官型共培养模型
PLoS One. 2022 Dec 1;17(12):e0276978. doi: 10.1371/journal.pone.0276978. eCollection 2022.
4
Genetic insight into Birt-Hogg-Dubé syndrome in Indian patients reveals novel mutations at FLCN.对印度患者的Birt-Hogg-Dubé综合征的遗传学洞察揭示了FLCN基因的新突变。
Orphanet J Rare Dis. 2022 Apr 27;17(1):176. doi: 10.1186/s13023-022-02326-5.
AMPK 激活促进肠道上皮细胞 Caco-2 中的紧密连接组装。
Int J Mol Sci. 2019 Oct 18;20(20):5171. doi: 10.3390/ijms20205171.
4
Folliculin regulates mTORC1/2 and WNT pathways in early human pluripotency.成纤维细胞生长因子受体底物 15 调节早期人类多能性中的 mTORC1/2 和 WNT 通路。
Nat Commun. 2019 Feb 7;10(1):632. doi: 10.1038/s41467-018-08020-0.
5
Metformin attenuates the effect of Staphylococcus aureus on airway tight junctions by increasing PKCζ-mediated phosphorylation of occludin.二甲双胍通过增加 PKCζ 介导的闭合蛋白磷酸化来减弱金黄色葡萄球菌对气道紧密连接的作用。
J Cell Mol Med. 2019 Jan;23(1):317-327. doi: 10.1111/jcmm.13929. Epub 2018 Nov 18.
6
AMPK in regulation of apical junctions and barrier function of intestinal epithelium.AMPK对肠上皮顶端连接和屏障功能的调节作用
Tissue Barriers. 2018;6(2):1-13. doi: 10.1080/21688370.2018.1487249. Epub 2018 Aug 21.
7
Free-Floating Mesothelial Cells in Pleural Fluid After Lung Surgery.肺手术后胸腔积液中的游离间皮细胞
Front Med (Lausanne). 2018 Apr 5;5:89. doi: 10.3389/fmed.2018.00089. eCollection 2018.
8
Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK.通过力介导的AMPK激活将E-钙黏蛋白机械转导与细胞代谢联系起来。
Nat Cell Biol. 2017 Jun;19(6):724-731. doi: 10.1038/ncb3537. Epub 2017 May 29.
9
Haploinsufficiency of the folliculin gene leads to impaired functions of lung fibroblasts in patients with Birt-Hogg-Dubé syndrome.卵泡抑素基因单倍剂量不足导致Birt-Hogg-Dubé综合征患者肺成纤维细胞功能受损。
Physiol Rep. 2016 Nov;4(21). doi: 10.14814/phy2.13025. Epub 2016 Nov 15.
10
Chronic AMPK activation via loss of FLCN induces functional beige adipose tissue through PGC-1α/ERRα.通过缺失卵泡抑素（FLCN）实现的慢性AMPK激活，经由过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）/雌激素相关受体α（ERRα）诱导功能性米色脂肪组织。
Genes Dev. 2016 May 1;30(9):1034-46. doi: 10.1101/gad.281410.116.