Mangoo-Karim R, Uchic M E, Grant M, Shumate W A, Calvet J P, Park C H, Grantham J J
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
FASEB J. 1989 Dec;3(14):2629-32. doi: 10.1096/fasebj.3.14.2480260.
Transepithelial fluid secretion has been postulated to account for the accumulation of fluid within hereditary and acquired renal cysts, but no such mechanism has been demonstrated in human kidney epithelium. It is shown here that transepithelial fluid secretion was stimulated by prostaglandin E1 (PGE1), forskolin, 8-Br-cyclic AMP, and 1-methyl-3-isobutylxanthine in polarized monolayers of established renal cell lines (MDCK and rat glomerular epithelial cells) and in monolayer cultures derived from the cyst walls of human autosomal dominant polycystic kidney disease and from epithelial cells of normal human renal cortex. Treatment with cyclic AMP agonists caused the same cells, when dispersed within a gel matrix of type I collagen (Vitrogen), to proliferate and form spherical fluid-filled monolayered cysts. Our findings suggest that increased intracellular cyclic AMP levels may have a critical role in the formation and expansion of hereditary and acquired renal cysts.
跨上皮液体分泌被认为是遗传性和获得性肾囊肿内液体蓄积的原因，但尚未在人肾上皮细胞中证实有这样的机制。本文显示，在已建立的肾细胞系（MDCK和大鼠肾小球上皮细胞）的极化单层培养物以及源自人类常染色体显性遗传性多囊肾囊肿壁和正常人肾皮质上皮细胞的单层培养物中，前列腺素E1（PGE1）、福司可林、8-溴环磷酸腺苷（8-Br-cyclic AMP）和1-甲基-3-异丁基黄嘌呤可刺激跨上皮液体分泌。用环磷酸腺苷激动剂处理后，当相同的细胞分散在I型胶原蛋白（维特罗生）的凝胶基质中时，它们会增殖并形成充满液体的球形单层囊肿。我们的研究结果表明，细胞内环磷酸腺苷水平升高可能在遗传性和获得性肾囊肿的形成和扩大中起关键作用。
