{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:32:17Z","timestamp":1791311537374,"version":"4.3.1"},"reference-count":33,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5608","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,2,7]]},"abstract":"<jats:p>The vascular endothelium was once thought to function primarily in nutrient and oxygen delivery, but recent evidence suggests that it may play a broader role in tissue homeostasis. To explore the role of sinusoidal endothelial cells (LSECs) in the adult liver, we studied the effects of vascular endothelial growth factor (VEGF) receptor activation on mouse hepatocyte growth. Delivery of VEGF-A increased liver mass in mice but did not stimulate growth of hepatocytes in vitro, unless LSECs were also present in the culture. Hepatocyte growth factor (HGF) was identified as one of the LSEC-derived paracrine mediators promoting hepatocyte growth. Selective activation of VEGF receptor\u20131 (VEGFR-1) stimulated hepatocyte but not endothelial proliferation in vivo and reduced liver damage in mice exposed to a hepatotoxin. Thus, VEGFR-1 agonists may have therapeutic potential for preservation of organ function in certain liver disorders.<\/jats:p>","DOI":"10.1126\/science.1079562","type":"journal-article","created":{"date-parts":[[2003,2,7]],"date-time":"2003-02-07T02:06:43Z","timestamp":1044583603000},"page":"890-893","source":"Crossref","is-referenced-by-count":584,"title":["Angiogenesis-Independent Endothelial Protection of Liver: Role of VEGFR-1"],"prefix":"10.1126","volume":"299","author":[{"given":"Jennifer","family":"LeCouter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk R.","family":"Moritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail Lewis","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Huan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Gerber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Hillan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Napoleone","family":"Ferrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","unstructured":"N. Simionescu M. Simionescu Endothelial Cell Dysfunctions (Plenum New York 1992).","DOI":"10.1007\/978-1-4899-0721-9"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063889"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1064344"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2479986"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1312256"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)90483-2"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.16.7533"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.18.1.0287"},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","unstructured":"J. E. Park H. H. Chen J. Winer K. A. Houck N. Ferrara J. Biol. Chem. 269 25646 (1994).","DOI":"10.1016\/S0021-9258(18)47298-5"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103213200"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.15.4064"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.8.3336.bloodjournal8783336"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1101-1194"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00821"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm731"},{"key":"e_1_3_1_17_2","unstructured":"See supporting data on Science Online."},{"key":"e_1_3_1_18_2","unstructured":"J. LeCouter et al. data not shown."},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/70928"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002016200"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.47.31273"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115568"},{"key":"e_1_3_1_23_2","first-page":"2683","volume":"9","author":"Yamane A.","year":"1994","unstructured":"Yamane A., et al., Oncogene 9, 2683 (1994).","journal-title":"Oncogene"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116451"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.60"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(95)80012-3"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90076-Q"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5291.1379"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006509200"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1004"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1080\/15216540252774784"},{"key":"e_1_3_1_32_2","unstructured":"J. LeCouter et al. unpublished data."},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/35091000"},{"key":"e_1_3_1_34_2","unstructured":"We thank C. Crowley for transfected CHO cells; B. Moffat for purification of VEGF mutants; J. Harris J. Kowalski L. DeGuzman Y. Li and M. van Hoy for animal studies; B. Wright for immunohistochemistry; G. Meng for enzyme-linked immunosorbent assay; R. Schwall for HGF antibodies; the Genentech Clinical Pathology lab for serum analysis; E. Stoelting for artwork; and  G. Frantz and F. Pealefor early in situ hybridization and morphological studies."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1079562","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T04:18:05Z","timestamp":1704860285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1079562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,2,7]]},"references-count":33,"journal-issue":{"issue":"5608","published-print":{"date-parts":[[2003,2,7]]}},"alternative-id":["10.1126\/science.1079562"],"URL":"https:\/\/doi.org\/10.1126\/science.1079562","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,2,7]]}}}