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进入常染色体显性遗传性多囊肾患者肝囊肿囊液的细胞因子和生长因子的分泌
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作者 Nichols M.T. gidey e. +2 位作者 Matzakos T. R.B. Doctor 雒向宁 《世界核心医学期刊文摘(胃肠病学分册)》 2005年第2期48-49,共2页
The principal extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD) involves formation of liver cysts derived from intrahepatic bil e ducts. Autocrine and paracrine factors secreted into the... The principal extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD) involves formation of liver cysts derived from intrahepatic bil e ducts. Autocrine and paracrine factors secreted into the cyst would be positio ned to modulate the rate of hepatic cyst growth. The aim of this study was to id entify potential growth factors present in human ADPKD liver cyst fluid. Cytokin e array and enzyme-linked immunosorbent assay analysis of human ADPKD liver cys t fluid detected epithelial neutrophil attractant 78, interleukin (IL)-6 (503 ±121 pg/mL); and IL-8 (4,488 ±355 pg/mL); and elevated levels of vascular end othelial growth factor compared with non-ADPKD bile (849 ±144 pg/mL vs. 270 pg /mL maximum concentration). ADPKD liver cyst cell cultures also released IL-8 a nd vascular endothelial growth factor, suggesting that cystic epithelial cells t hemselves are capable of secreting these factors. Western blotting of cultured c yst cells and immunostaining of intact cysts demonstrate that cysteine-X-cyste ine receptor 2, an epithelial neutrophil attractant 78 and IL-8 receptor, is ex pressed at the apical domain of cyst lining epithelial cells. Suggesting the cys tic epithelial cells may exist in hypoxic conditions, electron microscopy of the ADPKD liver cyst epithelium revealed morphological features similar to those ob served in ischemic bile ducts. These features include elongation, altered struct ure, and diminished abundance of apical microvilli. In conclusion, IL-8, epithe lial neutrophil attractant 78, IL-6, and vascular endothelial growth factor may serve as autocrine and paracrine factors to direct errant growth of ADPKD liver cyst epithelia. Interruption of these signaling pathways may provide therapeuti c targets for inhibiting liver cyst expansion. 展开更多
关键词 肝囊肿 细胞因子 生长因子 囊液 ADPKD 肾外表现 旁分泌因子 自分泌 免疫印迹 细胞培养
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