{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:08:40Z","timestamp":1793398120935,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,4,14]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Lymphatic vasculature constitutes a second vascular system essential for immune surveillance and tissue fluid homeostasis. Maturation of the hierarchical vascular structure, with a highly branched network of capillaries and ducts, is crucial for its function. Environmental cues mediate the remodeling process, but the mechanism that underlies this process is largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Polydom (also called Svep1) is an extracellular matrix protein identified as a high-affinity ligand for integrin \u03b19\u03b21. However, its physiological function is unclear. Here, we investigated the role of Polydom in lymphatic development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      We generated Polydom-deficient mice.\n                      <jats:italic>Polydom<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice showed severe edema and died immediately after birth because of respiratory failure. We found that although a primitive lymphatic plexus was formed, it failed to undergo remodeling in\n                      <jats:italic>Polydom<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      embryos, including sprouting of new capillaries and formation of collecting lymphatic vessels. Impaired lymphatic development was also observed after knockdown\/knockout of\n                      <jats:italic>polydom<\/jats:italic>\n                      in zebrafish. Polydom was deposited around lymphatic vessels, but secreted from surrounding mesenchymal cells. Expression of Foxc2 (forkhead box protein c2), a transcription factor involved in lymphatic remodeling, was decreased in\n                      <jats:italic>Polydom<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. Polydom bound to the lymphangiogenic factor Ang-2 (angiopoietin-2), which was found to upregulate Foxc2 expression in cultured lymphatic endothelial cells. Expressions of Tie1\/Tie2 receptors for angiopoietins were also decreased in\n                      <jats:italic>Polydom<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Polydom affects remodeling of lymphatic vessels in both mouse and zebrafish. Polydom deposited around lymphatic vessels seems to ensure Foxc2 upregulation in lymphatic endothelial cells, possibly via the Ang-2 and Tie1\/Tie2 receptor system.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.116.308825","type":"journal-article","created":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T21:10:23Z","timestamp":1486588223000},"page":"1276-1288","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":92,"title":["Polydom Is an Extracellular Matrix Protein Involved in Lymphatic Vessel Remodeling"],"prefix":"10.1161","volume":"120","author":[{"given":"Nanami","family":"Morooka","sequence":"first","affiliation":[{"name":"From the Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan (N. Morooka, S.F., R.S.-N., M.N., Y.T., C.S., I.N., K.S.); Laboratory of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, Japan (S.F.); Department of Cell Biology (M.N., H.N., N. Mochizuki) and AMED-CREST (N. Mochizuki), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sugiko","family":"Futaki","sequence":"additional","affiliation":[{"name":"From the Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan (N. Morooka, S.F., R.S.-N., M.N., Y.T., C.S., I.N., K.S.); Laboratory of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, Japan (S.F.); Department of Cell Biology (M.N., H.N., N. Mochizuki) and AMED-CREST (N. Mochizuki), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Sato-Nishiuchi","sequence":"additional","affiliation":[{"name":"From the Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan (N. Morooka, S.F., R.S.-N., M.N., Y.T., C.S., I.N., K.S.); Laboratory of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, Japan (S.F.); Department of Cell Biology (M.N., H.N., N. Mochizuki) and AMED-CREST (N. Mochizuki), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Nishino","sequence":"additional","affiliation":[{"name":"From the Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan (N. Morooka, S.F., R.S.-N., M.N., Y.T., C.S., I.N., K.S.); Laboratory of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, Japan (S.F.); Department of Cell Biology (M.N., H.N., N. Mochizuki) and AMED-CREST (N. Mochizuki), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Totani","sequence":"additional","affiliation":[{"name":"From the Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan (N. Morooka, S.F., R.S.-N., M.N., Y.T., C.S., I.N., K.S.); Laboratory of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, Japan (S.F.); Department of Cell Biology (M.N., H.N., N. Mochizuki) and AMED-CREST (N. Mochizuki), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisei","family":"Shimono","sequence":"additional","affiliation":[{"name":"From the Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan (N. Morooka, S.F., R.S.-N., M.N., Y.T., C.S., I.N., K.S.); Laboratory of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, Japan (S.F.); Department of Cell Biology (M.N., H.N., N. Mochizuki) and AMED-CREST (N. Mochizuki), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itsuko","family":"Nakano","sequence":"additional","affiliation":[{"name":"From the Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan (N. Morooka, S.F., R.S.-N., M.N., Y.T., C.S., I.N., K.S.); Laboratory of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, Japan (S.F.); Department of Cell Biology (M.N., H.N., N. Mochizuki) and AMED-CREST (N. Mochizuki), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"From the Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan (N. Morooka, S.F., R.S.-N., M.N., Y.T., C.S., I.N., K.S.); Laboratory of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, Japan (S.F.); Department of Cell Biology (M.N., H.N., N. Mochizuki) and AMED-CREST (N. 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