Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis.
Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis.
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淋巴管平滑肌瘤病肺组织淋巴内皮细胞的分离与表征。
DOI：
10.1038/s41598-021-88064-3
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发表时间：
2021-04-16
影响因子：
4.6
通讯作者：
Seyama K
中科院分区：
文献类型：
--
作者：
Nishino K;Yoshimatsu Y;Muramatsu T;Sekimoto Y;Mitani K;Kobayashi E;Okamoto S;Ebana H;Okada Y;Kurihara M;Suzuki K;Inazawa J;Takahashi K;Watabe T;Seyama K
淋巴管平滑肌瘤病（LAM）是一种罕见的肺部疾病，其特征是平滑肌样细胞（LAM细胞）的增殖和LAM病变中丰富的淋巴管。研究表明LAM细胞分泌的血管内皮生长因子D（VEGF-D）参与了LAM相关的淋巴管生成，但LAM病变中淋巴管生成的确切机制和淋巴管内皮细胞（LECs）的特性尚未阐明。在这项研究中，使用荧光激活细胞分选术（FACS）从受LAM影响的肺组织（LAM-LEC）和正常肺组织（对照LEC）中获得人原代培养的LEC。我们发现LAM-LEC的增殖和迁移能力明显高于对照LEC。VEGF-D能显著促进体外培养的LEC迁移，但对LEC增殖无明显影响。基因芯片和流式细胞仪分析显示，LAM-LEC中血管内皮生长因子受体（VEGFR）-3和整合素α9的表达增加。抑制VEGFR-3可抑制LEC的增殖和迁移，阻断整合素α9可减少VEGF-D诱导的LEC迁移。我们的数据揭示了LAM相关LEC的独特特征，增殖和迁移增加，这可能是由于VEGFR-3和整合素α9的高表达。此外，我们还发现VEGF-D/VEGFR-3和VEGF-D/ integrin α9信号通路在LAM相关淋巴管生成中起重要作用。
Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes to LAM-associated lymphangiogenesis, however, the precise mechanisms of lymphangiogenesis and characteristics of lymphatic endothelial cells (LECs) in LAM lesions have not yet been elucidated. In this study, human primary-cultured LECs were obtained both from LAM-affected lung tissues (LAM-LECs) and normal lung tissues (control LECs) using fluorescence-activated cell sorting (FACS). We found that LAM-LECs had significantly higher ability of proliferation and migration compared to control LECs. VEGF-D significantly promoted migration of LECs but not proliferation of LECs in vitro. cDNA microarray and FACS analysis revealed the expression of vascular endothelial growth factor receptor (VEGFR)-3 and integrin α9 were elevated in LAM-LECs. Inhibition of VEGFR-3 suppressed proliferation and migration of LECs, and blockade of integrin α9 reduced VEGF-D-induced migration of LECs. Our data uncovered the distinct features of LAM-associated LECs, increased proliferation and migration, which may be due to higher expression of VEGFR-3 and integrin α9. Furthermore, we also found VEGF-D/VEGFR-3 and VEGF-D/ integrin α9 signaling play an important role in LAM-associated lymphangiogenesis.
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影响因子：
3.3
作者：
Mishima, Koichi;Watabe, Tetsuro;Miyazono, Kohei
通讯作者：
Miyazono, Kohei
影响因子：
1.4
作者：
Seyama, Kuniaki;Kumasaka, Toshio;Sato, Teruhiko
通讯作者：
Sato, Teruhiko
影响因子：
--
作者：
Lorusso B;Falco A;Madeddu D;Frati C;Cavalli S;Graiani G;Gervasi A;Rinaldi L;Lagrasta C;Maselli D;Gnetti L;Silini EM;Quaini E;Ampollini L;Carbognani P;Quaini F
通讯作者：
Quaini F
DOI：
10.1056/nejmoa1100391
发表时间：
2011-04-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
McCormack FX;Inoue Y;Moss J;Singer LG;Strange C;Nakata K;Barker AF;Chapman JT;Brantly ML;Stocks JM;Brown KK;Lynch JP 3rd;Goldberg HJ;Young LR;Kinder BW;Downey GP;Sullivan EJ;Colby TV;McKay RT;Cohen MM;Korbee L;Taveira-DaSilva AM;Lee HS;Krischer JP;Trapnell BC;National Institutes of Health Rare Lung Diseases Consortium;MILES Trial Group
通讯作者：
MILES Trial Group
DOI：
10.1073/pnas.95.2.548
发表时间：
1998-01-20
影响因子：
11.1
作者：
Achen, MG;Jeltsch, M;Stacker, SA
通讯作者：
Stacker, SA