{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T15:50:09Z","timestamp":1778946609180,"version":"3.51.4"},"reference-count":26,"publisher":"Frontiers Media SA","issue":"10","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:p>Autosomal dominant polycystic kidney (ADPKD) is highly prevalent genetic disease. Liver cyst disease is the most common extrarenal manifestation in ADPKD and accounts for up to 10% of ADPKD morbidity and mortality. The clinical features of ADPKD liver disease arise from dramatic increases in liver cyst volumes. To identify mechanisms that promote liver cyst growth, the present study characterized the degree of vascularization of liver cyst walls and determined that cyst-specific cytokines and growth factors can drive endothelial cell proliferation and development. Microscopic techniques demonstrated liver cyst walls are well vascularized. A comparative analysis found the vascular density in free liver cyst walls was greater in mice than in humans. Treatment of human micro-vascular endothelial cells (HMEC-1) with human liver cyst fluid (huLCF) induced a rapid increase in vascular endothelium growth factor receptor 2 (VEGFR2) phosphorylation that persisted for 45\u201360 min and was blocked by 20 \u03bcM SU5416, a VEGFR tyrosine kinase inhibitor. Similarly, huLCF treatment of HMEC-1 cells induced an increase in the cell proliferation rate (131 \u00b1 6% of control levels; P &gt; 0.05) and the degree of vascular development (\u2018tube\u2019 diameter assay: 92 \u00b1 14 \u03bcm for huLCF vs. 12 \u00b1 7 \u03bcm for vehicle); P &gt; 0.05). Both cell proliferation and vascular development were sensitive to SU5416. These studies indicate that factors secreted by liver cyst epithelia can activate VEGF signaling pathways and induce endothelial cell proliferation and differentiation. The present studies suggest that targeting VEGFR2-dependent angiogenesis may be an effective therapeutic strategy in blocking ADPKD liver cyst vascularization and growth.<\/jats:p>","DOI":"10.3181\/0903-rm-112","type":"journal-article","created":{"date-parts":[[2009,7,13]],"date-time":"2009-07-13T21:10:08Z","timestamp":1247519408000},"page":"1155-1165","source":"Crossref","is-referenced-by-count":11,"title":["Liver Cyst Cytokines Promote Endothelial Cell Proliferation and Development"],"prefix":"10.3389","volume":"234","author":[{"given":"Kelley S.","family":"Brodsky","sequence":"first","affiliation":[{"name":"University of Colorado Health Sciences Center, Department of Medicine, Denver, Colorado 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan R.","family":"McWilliams","sequence":"additional","affiliation":[{"name":"University of Colorado Health Sciences Center, Department of Medicine, Denver, Colorado 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia R.","family":"Amura","sequence":"additional","affiliation":[{"name":"University of Colorado Health Sciences Center, Department of Medicine, Denver, Colorado 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas P.","family":"Barry","sequence":"additional","affiliation":[{"name":"University of Colorado Health Sciences Center, Department of Medicine, Denver, Colorado 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Brian","family":"Doctor","sequence":"additional","affiliation":[{"name":"University of Colorado Health Sciences Center, Department of Medicine, Denver, Colorado 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2009,10,1]]},"reference":[{"key":"bibr-R1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00080605"},{"key":"bibr-R2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMicm055470"},{"key":"bibr-R4","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006080835"},{"key":"bibr-R5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00203.x"},{"key":"bibr-R6","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840400413"},{"key":"bibr-R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00038.2007"},{"key":"bibr-R8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00457.2007"},{"key":"bibr-R9","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41997-7"},{"key":"bibr-R10","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.129.4.895"},{"key":"bibr-R11","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81570-6"},{"key":"bibr-R12","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21143"},{"key":"bibr-R13","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(02)00292-X"},{"key":"bibr-R14","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290514"},{"key":"bibr-R15","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12613748"},{"key":"bibr-R16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.264.4.C1003"},{"key":"bibr-R17","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.4.1375"},{"key":"bibr-R18","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6419com"},{"key":"bibr-R19","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E07-01-0004"},{"key":"bibr-R20","unstructured":"Fong TAT, Shawver LK, Sun L, Tang C, App H, Powell TJ, Kim YH, Schreck R, Wang X, Risau W, Ullrich A, Hirth KP, McMahon G. 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