Ectodomain Shedding of Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1) Is Induced by Vascular Endothelial Growth Factor A (VEGF-A)*
Identifieur interne : 008012 ( Ncbi/Checkpoint ); précédent : 008011; suivant : 008013Ectodomain Shedding of Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1) Is Induced by Vascular Endothelial Growth Factor A (VEGF-A)*
Auteurs : Hisayo Nishida-Fukuda ; Ryoichi Araki ; Masachika Shudou [Japon] ; Hidenori Okazaki ; Yasuko Tomono [Japon] ; Hironao Nakayama [Japon] ; Shinji Fukuda [Japon] ; Tomohisa Sakaue [Japon] ; Yuji Shirakata ; Koji Sayama ; Koji Hashimoto ; Michael Detmar [Suisse] ; Shigeki Higashiyama [Japon] ; Satoshi Hirakawa [Japon]Source :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2016.
Abstract
Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a type I transmembrane glycoprotein, is known as one of the most specific lymphatic vessel markers in the skin. In this study, we found that the ectodomain of LYVE-1 undergoes proteolytic cleavage, and this process produces soluble LYVE-1. We further identified the cleavage site for ectodomain shedding and generated an uncleavable mutant of LYVE-1. In lymphatic endothelial cells, ectodomain shedding of LYVE-1 was induced by vascular endothelial growth factor (VEGF)-A, an important factor for angiogenesis and lymphangiogenesis under pathological conditions. VEGF-A-induced LYVE-1 ectodomain shedding was mediated via the extracellular signal-regulated kinase (ERK) and a disintegrin and metalloproteinase (ADAM) 17. Wild-type LYVE-1, but not uncleavable LYVE-1, promoted migration of lymphatic endothelial cells in response to VEGF-A. Immunostaining analyses in human psoriasis skin lesions and VEGF-A transgenic mouse skin suggested that the ectodomain shedding of LYVE-1 occurred in lymphatic vessels undergoing chronic inflammation. These results indicate that the ectodomain shedding of LYVE-1 might be involved in promoting pathological lymphangiogenesis.
Url:
DOI: 10.1074/jbc.M115.683201
PubMed: 26966180
PubMed Central: 4865900
Affiliations:
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Ectodomain Shedding of Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1) Is Induced by Vascular Endothelial Growth Factor A (VEGF-A)<xref ref-type="fn" rid="FN1">*</xref>
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<author><name sortKey="Fukuda, Shinji" sort="Fukuda, Shinji" uniqKey="Fukuda S" first="Shinji" last="Fukuda">Shinji Fukuda</name>
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<author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name>
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<author><name sortKey="Higashiyama, Shigeki" sort="Higashiyama, Shigeki" uniqKey="Higashiyama S" first="Shigeki" last="Higashiyama">Shigeki Higashiyama</name>
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<author><name sortKey="Hirakawa, Satoshi" sort="Hirakawa, Satoshi" uniqKey="Hirakawa S" first="Satoshi" last="Hirakawa">Satoshi Hirakawa</name>
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<series><title level="j">The Journal of Biological Chemistry</title>
<idno type="ISSN">0021-9258</idno>
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<front><div type="abstract" xml:lang="en"><p>Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a type I transmembrane glycoprotein, is known as one of the most specific lymphatic vessel markers in the skin. In this study, we found that the ectodomain of LYVE-1 undergoes proteolytic cleavage, and this process produces soluble LYVE-1. We further identified the cleavage site for ectodomain shedding and generated an uncleavable mutant of LYVE-1. In lymphatic endothelial cells, ectodomain shedding of LYVE-1 was induced by vascular endothelial growth factor (VEGF)-A, an important factor for angiogenesis and lymphangiogenesis under pathological conditions. VEGF-A-induced LYVE-1 ectodomain shedding was mediated via the extracellular signal-regulated kinase (ERK) and a disintegrin and metalloproteinase (ADAM) 17. Wild-type LYVE-1, but not uncleavable LYVE-1, promoted migration of lymphatic endothelial cells in response to VEGF-A. Immunostaining analyses in human psoriasis skin lesions and VEGF-A transgenic mouse skin suggested that the ectodomain shedding of LYVE-1 occurred in lymphatic vessels undergoing chronic inflammation. These results indicate that the ectodomain shedding of LYVE-1 might be involved in promoting pathological lymphangiogenesis.</p>
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<name sortKey="Nishida Fukuda, Hisayo" sort="Nishida Fukuda, Hisayo" uniqKey="Nishida Fukuda H" first="Hisayo" last="Nishida-Fukuda">Hisayo Nishida-Fukuda</name>
<name sortKey="Okazaki, Hidenori" sort="Okazaki, Hidenori" uniqKey="Okazaki H" first="Hidenori" last="Okazaki">Hidenori Okazaki</name>
<name sortKey="Sayama, Koji" sort="Sayama, Koji" uniqKey="Sayama K" first="Koji" last="Sayama">Koji Sayama</name>
<name sortKey="Shirakata, Yuji" sort="Shirakata, Yuji" uniqKey="Shirakata Y" first="Yuji" last="Shirakata">Yuji Shirakata</name>
</noCountry>
<country name="Japon"><noRegion><name sortKey="Shudou, Masachika" sort="Shudou, Masachika" uniqKey="Shudou M" first="Masachika" last="Shudou">Masachika Shudou</name>
</noRegion>
<name sortKey="Fukuda, Shinji" sort="Fukuda, Shinji" uniqKey="Fukuda S" first="Shinji" last="Fukuda">Shinji Fukuda</name>
<name sortKey="Higashiyama, Shigeki" sort="Higashiyama, Shigeki" uniqKey="Higashiyama S" first="Shigeki" last="Higashiyama">Shigeki Higashiyama</name>
<name sortKey="Higashiyama, Shigeki" sort="Higashiyama, Shigeki" uniqKey="Higashiyama S" first="Shigeki" last="Higashiyama">Shigeki Higashiyama</name>
<name sortKey="Hirakawa, Satoshi" sort="Hirakawa, Satoshi" uniqKey="Hirakawa S" first="Satoshi" last="Hirakawa">Satoshi Hirakawa</name>
<name sortKey="Hirakawa, Satoshi" sort="Hirakawa, Satoshi" uniqKey="Hirakawa S" first="Satoshi" last="Hirakawa">Satoshi Hirakawa</name>
<name sortKey="Nakayama, Hironao" sort="Nakayama, Hironao" uniqKey="Nakayama H" first="Hironao" last="Nakayama">Hironao Nakayama</name>
<name sortKey="Nakayama, Hironao" sort="Nakayama, Hironao" uniqKey="Nakayama H" first="Hironao" last="Nakayama">Hironao Nakayama</name>
<name sortKey="Sakaue, Tomohisa" sort="Sakaue, Tomohisa" uniqKey="Sakaue T" first="Tomohisa" last="Sakaue">Tomohisa Sakaue</name>
<name sortKey="Tomono, Yasuko" sort="Tomono, Yasuko" uniqKey="Tomono Y" first="Yasuko" last="Tomono">Yasuko Tomono</name>
</country>
<country name="Suisse"><noRegion><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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