cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells
cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells
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DOI：
10.1681/asn.v1171179
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发表时间：
2000-07-01
影响因子：
13.6
通讯作者：
Guggino, WB
中科院分区：
文献类型：
--
作者：
Hanaoka, K;Guggino, WB
在常染色体显性遗传性多囊肾病(ADPKD)中，上皮细胞的增殖和积液都是导致囊性生长的原因。先前报道囊性纤维化跨膜电导调节因子(CFTR)在ADPKD患者的囊中表达，提示cAMP刺激的Cl-和液体分泌通过CFTR发生。本研究的目的是研究细胞增殖在ADPKD囊性形成中的作用，并进一步探讨分泌液在囊性生长中的作用。原代培养ADPKD上皮细胞和从皮质分离的正常肾上皮细胞的混合群体(HRCE细胞)。这项研究测试了cAMP是否同时参与刺激细胞增殖和体外囊泡的形成。H-3-胸腺嘧啶核苷掺入实验表明，表皮生长因子可刺激ADPKD细胞和HRCE细胞的增殖。此外，cAMP可促进ADPKD细胞的DNA合成和细胞增殖，但不能刺激HRCE细胞的增殖。CAMP和表皮生长因子对ADPKD细胞生长的影响是相加的。CAMP还可刺激ADPKD细胞囊泡增大和液体分泌。相反，在没有cAMP的情况下，HRCE细胞的囊泡形成和增大发生。在ADPKD细胞中，二苯胺羧酸(DPC)和格列本脲可阻断囊腔内液体的分泌，而在HRCE细胞中，DPC仅可阻断囊腔内液体的分泌。本研究表明ADPKD细胞具有独特的特性，cAMP刺激液体分泌和细胞增殖，提示cAMP在ADPKD过程中对囊壁生长起着非常重要的作用。
Both epithelial cell proliferation and fluid accumulation are responsible for cyst growth in autosomal dominant polycystic kidney disease (ADPKD). It was previously reported that the cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in cysts from ADPKD patients and suggested that cAMP-stimulated Cl- and fluid secretion occurs through CFTR. The purpose of this study was to investigate the role of cell proliferation in cyst formation in ADPKD and to explore further the role of fluid secretion in cyst growth. Primary cultures both of ADPKD epithelial cells and a mixed population of normal renal epithelial cells isolated from the cortex (HRCE cells) were used. This study tested whether cAMP was involved both in stimulating cell proliferation and formation of cysts in vitro. H-3-Thymidine incorporation assays showed that epidermal growth factor stimulated proliferation both in ADPKD cells and HRCE cells. In addition, cAMP stimulated DNA synthesis and cell proliferation in ADPKD, but not HRCE, cells. The effects of cAMP and epidermal growth factor on cell growth in ADPKD cells were additive. cAMP also stimulated cyst enlargement and fluid secretion in ADPKD cells. By contrast, cyst formation and enlargement from HRCE cells occurred without cAMP. Fluid secretion into the cyst lumen was blocked by diphenylamine carboxylic acid (DPC) and glibenclamide in ADPKD cells but blocked only by DPC in HRCE cells. This study showed that ADPKD cells have unique characteristics; cAMP stimulates fluid secretion and cell proliferation, indicating cAMP plays a very important role in cyst growth during the course of ADPKD.