{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:10:52Z","timestamp":1791263452121,"version":"4.1.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p> The hereditary von Hippel-Lindau (VHL) syndrome predisposes sufferers to highly vascularized tumors such as renal clear cell carcinoma (RCC) and central nervous system hemangioblastoma. In RCC4 and RCC786\u20130 VHL<jats:sup>\u2212<\/jats:sup> cells with VHL mutations, the protein of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) is constitutively stabilized and the mRNA levels of HIF target genes, including vascular endothelial growth factor (VEGF), are elevated. However, the expression of angiopoietins in these cells and their involvement in angiogenesis are not well known. In this study, we compared the mRNA levels of angiopoietins in human kidney proximal tubule epithelial (RPTE) and RCC4 and RCC786\u20130 VHL<jats:sup>\u2212<\/jats:sup> cells. In RPTE cells, angiopoietin-4 (Ang-4) expression was selectively induced by hypoxia or by expression of a hybrid form of HIF-1\u03b1. Under normoxic conditions, the mRNA levels of Ang-4 were higher in RCC4 and RCC786\u20130 VHL<jats:sup>\u2212<\/jats:sup> than RPTE cells. Angiopoietin-1 expression was detectable in RCC4 and RCC786\u20130 VHL<jats:sup>\u2212<\/jats:sup> cells but not RPTE cells. In RCC786\u20130 VHL<jats:sup>+<\/jats:sup> cells, which were stably transfected with a wild-type copy of VHL, the mRNA levels of VEGF and Ang-4 were suppressed and the hypoxic response was restored. We also demonstrated that stimulation of endothelial tube formation by conditioned medium harvested from RCC4 cells was inhibited by a soluble Tie-2 receptor. These results suggest that the angiopoietin\/Tie-2 system may participate in the angiogenic response to hypoxia in renal tissues and in tumor angiogenesis in renal carcinoma. <\/jats:p>","DOI":"10.1152\/ajprenal.00028.2004","type":"journal-article","created":{"date-parts":[[2004,6,16]],"date-time":"2004-06-16T20:23:49Z","timestamp":1087417429000},"page":"F649-F657","source":"Crossref","is-referenced-by-count":48,"title":["Expression of angiopoietins in renal epithelial and clear cell carcinoma cells: regulation by hypoxia and participation in angiogenesis"],"prefix":"10.1152","volume":"287","author":[{"given":"Midori","family":"Yamakawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis X.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J.","family":"Belanger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Date","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Kuriyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seng H.","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Gregory","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canwen","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.281.3.L582"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.3.233"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2002.2021"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(01)82003-0"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1002\/path.1228"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81812-7"},{"key":"R7","unstructured":"Davis S and Yancopoulos GD. 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