RENAL EPITHELIAL CYST FORMATION AND ENLARGEMENT INVITRO - DEPENDENCE ON CAMP
RENAL EPITHELIAL CYST FORMATION AND ENLARGEMENT INVITRO - DEPENDENCE ON CAMP
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DOI：
10.1073/pnas.86.15.6007
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发表时间：
1989-08-01
影响因子：
11.1
通讯作者：
GRANTHAM, JJ
中科院分区：
文献类型：
--
作者：
MANGOOKARIM, R;UCHIC, M;GRANTHAM, JJ
囊肿是一种常见的肾脏异常，是由连续的一层上皮细胞包裹的尿样液体的集合。肾囊肿起源于肾单位和集合管，随着上皮细胞的增殖和跨上皮液的分泌而逐渐增大。包囊形成的起因和控制包囊扩大的因素尚不清楚。我们使用体外肾囊肿模型来探讨cAMP信号转导系统在囊肿形成和扩张中的作用。当前列腺素E_1、精氨酸加压素、霍乱毒素、Forsklin或8-溴腺苷3‘’，5‘-环磷酸增加细胞内cAMP时，在水合胶原凝胶中培养的MDCK细胞产生极化的单层上皮囊。所有激动剂都被核苷酸磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤增强。CAMP激动剂可加速囊泡扩大的细胞增殖成分，表现为MDCK细胞在融合下单层的生长增加。细胞外基质中cAMP激动剂可刺激体液分泌成分，反映为体液跨上皮跨膜运动，细胞生长于可渗透载体上。囊液和分泌液中的氯含量高于洗浴介质。结论：MDCK囊性病变的发生发展依赖于cAMP。该信号转导系统可能是肾脏上皮细胞增殖和跨上皮液分泌的重要调节因子。
Cysts, a common abnormality of kidneys, are collections of urine-like fluid enclosed by a continuous layer of epithelial cells. Renal cysts derive from nephrons and collecting ducts and progressively enlarge as a consequence of epithelial proliferation and transepithelial fluid secretion. The initiation of cyst formation and the factors that control cyst enlargement are unknown. We used an in vitro model of renal cysts to explore the role of the cAMP signal transduction system in the formation and expansion of cysts. MDCK cells, cultured in hydrated-collagen gel, produced polarized monolayered epithelial cysts when intracellular cAMP was increased by prostaglandin E1, arginine vasopressin, cholera toxin, forskolin, or 8-bromoadenosine 3'',5''-cyclic monophosphate. All agonists were potentiated by 3-isobutyl-1-methylxanthine, a nucleotide phosphodiesterase inhibitor. The cell proliferation component of cyst enlargement was accelerated by cAMP agonists, as shown by the increased growth of MDCK cells in subconfluent monolayers. The fluid secretion component, reflected by the transepithelial movement of fluid across polarized monolayers of MDCK cells grown on permeable supports, was stimulated by cAMP agonists in the basolateral medium. Chloride levels were higher in the cyst fluid and the secreted fluid than in the bathing medium. We conclude that the development of MDCK cysts is dependent on cAMP. This signal transduction system may be an important modulator of epithelial cell proliferation and transepithelial fluid secretion in the kidney.