{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:38:20Z","timestamp":1791203900568,"version":"4.2.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lymphangiogensis is involved in various pathological conditions, such as arthritis and cancer metastasis. Although many factors have been identified to stimulate lymphatic vessel growth, little is known about lymphangiogenesis inhibitors. Here we report that membrane type 1-matrix metalloproteinase (MT1-MMP) is an endogenous suppressor of lymphatic vessel growth. MT1-MMP-deficient mice exhibit spontaneous corneal lymphangiogenesis without concomitant changes in angiogenesis. Mice lacking MT1-MMP in either lymphatic endothelial cells or macrophages recapitulate corneal lymphangiogenic phenotypes observed in <jats:italic>Mmp14<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, suggesting that the spontaneous lymphangiogenesis is both lymphatic endothelial cells autonomous and macrophage associated. Mechanistically, MT1-MMP directly cleaves LYVE-1 on lymphatic endothelial cells to inhibit LYVE-1-mediated lymphangiogenic responses. In addition, MT1-MMP-mediated PI3K\u03b4 signalling restrains the production of VEGF-C from prolymphangiogenic macrophages through repressing the activation of NF-\u03baB signalling. Thus, we identify MT1-MMP as an endogenous inhibitor of physiological lymphangiogenesis.<\/jats:p>","DOI":"10.1038\/ncomms10824","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T10:43:36Z","timestamp":1456829016000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["MT1-MMP sheds LYVE-1 on lymphatic endothelial cells and suppresses VEGF-C production to inhibit lymphangiogenesis"],"prefix":"10.1038","volume":"7","author":[{"given":"Hoi Leong Xavier","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renhai","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihai","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"BFncomms10824_CR1","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.cell.2010.01.045","volume":"140","author":"T Tammela","year":"2010","unstructured":"Tammela, T. & Alitalo, K. Lymphangiogenesis: molecular mechanisms and future promise. Cell 140, 460\u2013476 (2010).","journal-title":"Cell"},{"key":"BFncomms10824_CR2","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1196\/annals.1413.020","volume":"1131","author":"MG Achen","year":"2008","unstructured":"Achen, M. G. & Stacker, S. A. Molecular control of lymphatic metastasis. Ann. N. Y. Acad. Sci. 1131, 225\u2013234 (2008).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"BFncomms10824_CR3","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nrc3677","volume":"14","author":"SA Stacker","year":"2014","unstructured":"Stacker, S. A. et al. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat. Rev. Cancer 14, 159\u2013172 (2014).","journal-title":"Nat. Rev. Cancer"},{"key":"BFncomms10824_CR4","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1083\/jcb.144.4.789","volume":"144","author":"S Banerji","year":"1999","unstructured":"Banerji, S. et al. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J. Cell Biol. 144, 789\u2013801 (1999).","journal-title":"J. Cell Biol."},{"key":"BFncomms10824_CR5","doi-asserted-by":"publisher","first-page":"e92857","DOI":"10.1371\/journal.pone.0092857","volume":"9","author":"M Wu","year":"2014","unstructured":"Wu, M. et al. Low molecular weight hyaluronan induces lymphangiogenesis through LYVE-1-mediated signaling pathways. PLoS ONE 9, e92857 (2014).","journal-title":"PLoS ONE"},{"key":"BFncomms10824_CR6","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/ni1013","volume":"5","author":"MJ Karkkainen","year":"2004","unstructured":"Karkkainen, M. J. et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat. Immunol. 5, 74\u201380 (2004).","journal-title":"Nat. Immunol."},{"key":"BFncomms10824_CR7","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1172\/JCI15830","volume":"111","author":"YS Yoon","year":"2003","unstructured":"Yoon, Y. S. et al. VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema. J. Clin. Invest. 111, 717\u2013725 (2003).","journal-title":"J. Clin. Invest."},{"key":"BFncomms10824_CR8","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1093\/emboj\/20.6.1223","volume":"20","author":"T Veikkola","year":"2001","unstructured":"Veikkola, T. et al. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J. 20, 1223\u20131231 (2001).","journal-title":"EMBO J."},{"key":"BFncomms10824_CR9","doi-asserted-by":"publisher","first-page":"15894","DOI":"10.1073\/pnas.1208324109","volume":"109","author":"R Cao","year":"2012","unstructured":"Cao, R. et al. Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis. Proc. Natl Acad. Sci. USA 109, 15894\u201315899 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms10824_CR10","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/nprot.2011.359","volume":"6","author":"R Cao","year":"2011","unstructured":"Cao, R. et al. Mouse corneal lymphangiogenesis model. Nat. Protoc. 6, 817\u2013826 (2011).","journal-title":"Nat. Protoc."},{"key":"BFncomms10824_CR11","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1002\/j.1460-2075.1996.tb00521.x","volume":"15","author":"V Joukov","year":"1996","unstructured":"Joukov, V. et al. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 15, 1751 (1996).","journal-title":"EMBO J."},{"key":"BFncomms10824_CR12","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1242\/dev.122.12.3829","volume":"122","author":"E Kukk","year":"1996","unstructured":"Kukk, E. et al. VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development 122, 3829\u20133837 (1996).","journal-title":"Development"},{"key":"BFncomms10824_CR13","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1073\/pnas.95.2.548","volume":"95","author":"MG Achen","year":"1998","unstructured":"Achen, M. G. et al. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc. Natl Acad. Sci. USA 95, 548\u2013553 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms10824_CR14","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.semcdb.2007.06.008","volume":"19","author":"MV Barbolina","year":"2008","unstructured":"Barbolina, M. V. & Stack, M. S. Membrane type 1-matrix metalloproteinase: substrate diversity in pericellular proteolysis. Semin. Cell Dev. Biol. 19, 24\u201333 (2008).","journal-title":"Semin. Cell Dev. Biol."},{"key":"BFncomms10824_CR15","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0092-8674(00)80064-1","volume":"99","author":"K Holmbeck","year":"1999","unstructured":"Holmbeck, K. et al. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99, 81\u201392 (1999).","journal-title":"Cell"},{"key":"BFncomms10824_CR16","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1016\/j.devcel.2012.04.014","volume":"22","author":"KM Chan","year":"2012","unstructured":"Chan, K. M. et al. MT1-MMP inactivates ADAM9 to regulate FGFR2 signaling and calvarial osteogenesis. Dev. Cell 22, 1176\u20131190 (2012).","journal-title":"Dev. Cell"},{"key":"BFncomms10824_CR17","doi-asserted-by":"publisher","first-page":"4052","DOI":"10.1073\/pnas.060037197","volume":"97","author":"Z Zhou","year":"2000","unstructured":"Zhou, Z. et al. Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc. Natl Acad. Sci. USA 97, 4052\u20134057 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms10824_CR18","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.cell.2006.02.050","volume":"125","author":"TH Chun","year":"2006","unstructured":"Chun, T. H. et al. A pericellular collagenase directs the 3-dimensional development of white adipose tissue. Cell 125, 577\u2013591 (2006).","journal-title":"Cell"},{"key":"BFncomms10824_CR19","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/emboj.2011.136","volume":"30","author":"G Jin","year":"2011","unstructured":"Jin, G. et al. MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell development. EMBO J. 30, 2281\u20132293 (2011).","journal-title":"EMBO J."},{"key":"BFncomms10824_CR20","doi-asserted-by":"publisher","first-page":"5405","DOI":"10.1182\/blood-2011-11-390849","volume":"119","author":"C Nishida","year":"2012","unstructured":"Nishida, C. et al. MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated chemokine\/cytokine gene transcription within niche cells. Blood 119, 5405\u20135416 (2012).","journal-title":"Blood"},{"key":"BFncomms10824_CR21","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.ajhg.2012.07.022","volume":"91","author":"BR Evans","year":"2012","unstructured":"Evans, B. R. et al. Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome. Am. J. Hum. Genet. 91, 572\u2013576 (2012).","journal-title":"Am. J. Hum. Genet."},{"key":"BFncomms10824_CR22","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.4161\/cc.20949","volume":"11","author":"HL Wong","year":"2012","unstructured":"Wong, H. L. et al. When MT1-MMP meets ADAMs. Cell Cycle 11, 2793\u20132798 (2012).","journal-title":"Cell Cycle"},{"key":"BFncomms10824_CR23","doi-asserted-by":"publisher","first-page":"4481","DOI":"10.1096\/fj.12-205906","volume":"26","author":"A Koziol","year":"2012","unstructured":"Koziol, A. et al. The protease MT1-MMP drives a combinatorial proteolytic program in activated endothelial cells. FASEB J. 26, 4481\u20134494 (2012).","journal-title":"FASEB J."},{"key":"BFncomms10824_CR24","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/path.1942","volume":"209","author":"K Schledzewski","year":"2006","unstructured":"Schledzewski, K. et al. Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4\/80+, CD11b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangiogenesis. J. Pathol. 209, 67\u201377 (2006).","journal-title":"J. Pathol."},{"key":"BFncomms10824_CR25","doi-asserted-by":"publisher","first-page":"e0131952","DOI":"10.1371\/journal.pone.0131952","volume":"10","author":"S Kumar","year":"2015","unstructured":"Kumar, S., Ratnikov, B. I., Kazanov, M. D., Smith, J. W. & Cieplak, P. Correction: CleavPredict: a platform for reasoning about matrix metalloproteinases proteolytic events. PLoS ONE 10, e0131952 (2015).","journal-title":"PLoS ONE"},{"key":"BFncomms10824_CR26","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1182\/blood-2012-08-450502","volume":"121","author":"N Platonova","year":"2013","unstructured":"Platonova, N. et al. Evidence for the interaction of fibroblast growth factor-2 with the lymphatic endothelial cell marker LYVE-1. Blood 121, 1229\u20131237 (2013).","journal-title":"Blood"},{"key":"BFncomms10824_CR27","doi-asserted-by":"publisher","first-page":"29420","DOI":"10.1074\/jbc.M301885200","volume":"278","author":"LY Bourguignon","year":"2003","unstructured":"Bourguignon, L. Y., Singleton, P. A., Zhu, H. & Diedrich, F. Hyaluronan-mediated CD44 interaction with RhoGEF and Rho kinase promotes Grb2-associated binder-1 phosphorylation and phosphatidylinositol 3-kinase signaling leading to cytokine (macrophage-colony stimulating factor) production and breast tumor progression. J. Biol. Chem. 278, 29420\u201329434 (2003).","journal-title":"J. Biol. Chem."},{"key":"BFncomms10824_CR28","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1172\/JCI23874","volume":"115","author":"K Maruyama","year":"2005","unstructured":"Maruyama, K. et al. Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J. Clin. Invest. 115, 2363\u20132372 (2005).","journal-title":"J. Clin. Invest."},{"key":"BFncomms10824_CR29","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1172\/JCI20465","volume":"113","author":"C Cursiefen","year":"2004","unstructured":"Cursiefen, C. et al. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J. Clin. Invest. 113, 1040\u20131050 (2004).","journal-title":"J. Clin. Invest."},{"key":"BFncomms10824_CR30","doi-asserted-by":"publisher","first-page":"5650","DOI":"10.1182\/blood-2008-09-176776","volume":"113","author":"RP Kataru","year":"2009","unstructured":"Kataru, R. P. et al. Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution. Blood 113, 5650\u20135659 (2009).","journal-title":"Blood"},{"key":"BFncomms10824_CR31","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/S0002-9440(10)64255-1","volume":"161","author":"SF Schoppmann","year":"2002","unstructured":"Schoppmann, S. F. et al. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am. J. Pathol. 161, 947\u2013956 (2002).","journal-title":"Am. J. Pathol."},{"key":"BFncomms10824_CR32","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1016\/j.bbrc.2008.10.077","volume":"377","author":"K Watari","year":"2008","unstructured":"Watari, K. et al. Role of macrophages in inflammatory lymphangiogenesis: enhanced production of vascular endothelial growth factor C and D through NF-kappaB activation. Biochem. Biophys. Res. Commun. 377, 826\u2013831 (2008).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFncomms10824_CR33","doi-asserted-by":"publisher","first-page":"e7067","DOI":"10.1371\/journal.pone.0007067","volume":"4","author":"A Zumsteg","year":"2009","unstructured":"Zumsteg, A. et al. Myeloid cells contribute to tumor lymphangiogenesis. PLoS ONE 4, e7067 (2009).","journal-title":"PLoS ONE"},{"key":"BFncomms10824_CR34","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1101\/gad.178749.111","volume":"26","author":"R Shimizu-Hirota","year":"2012","unstructured":"Shimizu-Hirota, R. et al. MT1-MMP regulates the PI3Kdelta.Mi-2\/NuRD-dependent control of macrophage immune function. Genes Dev. 26, 395\u2013413 (2012).","journal-title":"Genes Dev."},{"key":"BFncomms10824_CR35","doi-asserted-by":"publisher","first-page":"e31794","DOI":"10.1371\/journal.pone.0031794","volume":"7","author":"KL Hall","year":"2012","unstructured":"Hall, K. L., Volk-Draper, L. D., Flister, M. J. & Ran, S. New model of macrophage acquisition of the lymphatic endothelial phenotype. PLoS ONE 7, e31794 (2012).","journal-title":"PLoS ONE"},{"key":"BFncomms10824_CR36","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.immuni.2014.01.013","volume":"40","author":"Y Zhang","year":"2014","unstructured":"Zhang, Y. et al. Activation of vascular endothelial growth factor receptor-3 in macrophages restrains TLR4-NF-kappaB signaling and protects against endotoxin shock. Immunity 40, 501\u2013514 (2014).","journal-title":"Immunity"},{"key":"BFncomms10824_CR37","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nrm2882","volume":"11","author":"B Vanhaesebroeck","year":"2010","unstructured":"Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M. & Bilanges, B. The emerging mechanisms of isoform-specific PI3K signalling. Nat. Rev. Mol. Cell Biol. 11, 329\u2013341 (2010).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFncomms10824_CR38","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","volume":"27","author":"CA Dinarello","year":"2009","unstructured":"Dinarello, C. A. Immunological and inflammatory functions of the interleukin-1 family. Annu. Rev. Immunol. 27, 519\u2013550 (2009).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms10824_CR39","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1038\/ni.2426","volume":"13","author":"E Aksoy","year":"2012","unstructured":"Aksoy, E. et al. The p110delta isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock. Nat. Immunol. 13, 1045\u20131054 (2012).","journal-title":"Nat. Immunol."},{"key":"BFncomms10824_CR40","doi-asserted-by":"publisher","first-page":"13491","DOI":"10.1074\/jbc.M708055200","volume":"283","author":"Q Zhang","year":"2008","unstructured":"Zhang, Q. et al. VEGF-C, a lymphatic growth factor, is a RANKL target gene in osteoclasts that enhances osteoclastic bone resorption through an autocrine mechanism. J. Biol. Chem. 283, 13491\u201313499 (2008).","journal-title":"J. Biol. Chem."},{"key":"BFncomms10824_CR41","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1146\/annurev.immunol.021908.132641","volume":"27","author":"S Vallabhapurapu","year":"2009","unstructured":"Vallabhapurapu, S. & Karin, M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu. Rev. Immunol. 27, 693\u2013733 (2009).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms10824_CR42","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1128\/MCB.01503-06","volume":"27","author":"NW Gale","year":"2007","unstructured":"Gale, N. W. et al. Normal lymphatic development and function in mice deficient for the lymphatic hyaluronan receptor LYVE-1. Mol. Cell. Biol. 27, 595\u2013604 (2007).","journal-title":"Mol. Cell. Biol."},{"key":"BFncomms10824_CR43","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.4049\/jimmunol.163.9.4917","volume":"163","author":"U Protin","year":"1999","unstructured":"Protin, U., Schweighoffer, T., Jochum, W. & Hilberg, F. CD44-deficient mice develop normally with changes in subpopulations and recirculation of lymphocyte subsets. J. Immunol. 163, 4917\u20134923 (1999).","journal-title":"J. Immunol."},{"key":"BFncomms10824_CR44","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/nrc3023","volume":"11","author":"M Zoller","year":"2011","unstructured":"Zoller, M. CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat. Rev. Cancer 11, 254\u2013267 (2011).","journal-title":"Nat. Rev. Cancer"},{"key":"BFncomms10824_CR45","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1161\/CIRCULATIONAHA.114.011096","volume":"130","author":"Q Wei","year":"2014","unstructured":"Wei, Q. et al. CD82 restrains pathological angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells. Circulation 130, 1493\u20131504 (2014).","journal-title":"Circulation"},{"key":"BFncomms10824_CR46","doi-asserted-by":"publisher","first-page":"19420","DOI":"10.1074\/jbc.M011004200","volume":"276","author":"R Prevo","year":"2001","unstructured":"Prevo, R., Banerji, S., Ferguson, D. J., Clasper, S. & Jackson, D. G. Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium. J. Biol. Chem. 276, 19420\u201319430 (2001).","journal-title":"J. Biol. Chem."},{"key":"BFncomms10824_CR47","doi-asserted-by":"publisher","first-page":"10195","DOI":"10.1074\/jbc.M112.447169","volume":"288","author":"S Ingvarsen","year":"2013","unstructured":"Ingvarsen, S. et al. Targeting a single function of the multifunctional matrix metalloprotease MT1-MMP: impact on lymphangiogenesis. J. Biol. Chem. 288, 10195\u201310204 (2013).","journal-title":"J. Biol. Chem."},{"key":"BFncomms10824_CR48","doi-asserted-by":"publisher","first-page":"5048","DOI":"10.1182\/blood-2011-12-400267","volume":"119","author":"B Detry","year":"2012","unstructured":"Detry, B. et al. Matrix metalloproteinase-2 governs lymphatic vessel formation as an interstitial collagenase. Blood 119, 5048\u20135056 (2012).","journal-title":"Blood"},{"key":"BFncomms10824_CR49","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1038\/nm.2018","volume":"15","author":"RJ Albuquerque","year":"2009","unstructured":"Albuquerque, R. J. et al. Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat. Med. 15, 1023\u20131030 (2009).","journal-title":"Nat. Med."},{"key":"BFncomms10824_CR50","doi-asserted-by":"publisher","first-page":"4242","DOI":"10.1182\/blood-2012-08-453043","volume":"121","author":"N Singh","year":"2013","unstructured":"Singh, N. et al. Soluble vascular endothelial growth factor receptor-3 is essential for corneal alymphaticity. Blood 121, 4242\u20134249 (2013).","journal-title":"Blood"},{"key":"BFncomms10824_CR51","first-page":"2954","volume":"119","author":"P Baluk","year":"2009","unstructured":"Baluk, P. et al. TNF-alpha drives remodeling of blood vessels and lymphatics in sustained airway inflammation in mice. J. Clin. Invest. 119, 2954\u20132964 (2009).","journal-title":"J. Clin. Invest."},{"key":"BFncomms10824_CR52","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1084\/jem.20081605","volume":"206","author":"Y Kubota","year":"2009","unstructured":"Kubota, Y. et al. M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J. Exp. Med. 206, 1089\u20131102 (2009).","journal-title":"J. Exp. Med."},{"key":"BFncomms10824_CR53","first-page":"2264","volume":"43","author":"CS Brissette-Storkus","year":"2002","unstructured":"Brissette-Storkus, C. S., Reynolds, S. M., Lepisto, A. J. & Hendricks, R. L. Identification of a novel macrophage population in the normal mouse corneal stroma. Invest. Ophthalmol. Vis. Sci. 43, 2264\u20132271 (2002).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"BFncomms10824_CR54","doi-asserted-by":"publisher","first-page":"ra75","DOI":"10.1126\/scisignal.2001868","volume":"4","author":"R Merline","year":"2011","unstructured":"Merline, R. et al. Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and MicroRNA-21. Sci. Signal. 4, ra75 (2011).","journal-title":"Sci. Signal."},{"key":"BFncomms10824_CR55","first-page":"1957","volume":"39","author":"JL Funderburgh","year":"1998","unstructured":"Funderburgh, J. L. et al. Decorin and biglycan of normal and pathologic human corneas. Invest. Ophthalmol. Vis. Sci. 39, 1957\u20131964 (1998).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"BFncomms10824_CR56","doi-asserted-by":"publisher","first-page":"110","DOI":"10.2174\/156652411794859241","volume":"11","author":"RR Mohan","year":"2011","unstructured":"Mohan, R. R., Tovey, J. C., Gupta, R., Sharma, A. & Tandon, A. Decorin biology, expression, function and therapy in the cornea. Curr. Mol. Med. 11, 110\u2013128 (2011).","journal-title":"Curr. Mol. Med."},{"key":"BFncomms10824_CR57","doi-asserted-by":"publisher","first-page":"4944","DOI":"10.1038\/ncomms5944","volume":"5","author":"H Ji","year":"2014","unstructured":"Ji, H. et al. TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling. Nat. Commun. 5, 4944 (2014).","journal-title":"Nat. Commun."},{"key":"BFncomms10824_CR58","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nrc745","volume":"2","author":"M Egeblad","year":"2002","unstructured":"Egeblad, M. & Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2, 161\u2013174 (2002).","journal-title":"Nat. Rev. Cancer"},{"key":"BFncomms10824_CR59","first-page":"e50193","volume":"73","author":"N An","year":"2013","unstructured":"An, N. & Kang, Y. Using quantitative real-time PCR to determine donor cell engraftment in a competitive murine bone marrow transplantation model. J. Vis. Exp. 73, e50193 (2013).","journal-title":"J. Vis. Exp."},{"key":"BFncomms10824_CR60","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1038\/nprot.2010.113","volume":"5","author":"ME Pitulescu","year":"2010","unstructured":"Pitulescu, M. E., Schmidt, I., Benedito, R. & Adams, R. H. Inducible gene targeting in the neonatal vasculature and analysis of retinal angiogenesis in mice. Nat. Protoc. 5, 1518\u20131534 (2010).","journal-title":"Nat. Protoc."},{"key":"BFncomms10824_CR61","doi-asserted-by":"publisher","first-page":"12325","DOI":"10.1073\/pnas.1102789108","volume":"108","author":"V Krishnan","year":"2011","unstructured":"Krishnan, V. et al. Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proc. Natl Acad. Sci. USA 108, 12325\u201312330 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms10824.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms10824","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms10824.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T11:45:15Z","timestamp":1672832715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms10824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,1]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,22]]}},"alternative-id":["BFncomms10824"],"URL":"https:\/\/doi.org\/10.1038\/ncomms10824","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,1]]},"assertion":[{"value":"29 March 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10824"}}