Pentoxifylline inhibits human peritoneal mesothelial cell growth and collagen synthesis:: Effects on TGF-β
Pentoxifylline inhibits human peritoneal mesothelial cell growth and collagen synthesis:: Effects on TGF-β
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DOI：
10.1046/j.1523-1755.2000.00123.x
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发表时间：
2000-06-01
影响因子：
19.6
通讯作者：
Hsieh, BS
中科院分区：
文献类型：
--
作者：
Fang, CC;Yen, CJ;Hsieh, BS
背景腹膜纤维化综合征的预防和治疗已成为持续性非卧床腹膜透析（CAPD）患者的重要问题。最近的证据表明，间皮干细胞增殖和基质过度生产倾向于腹膜纤维化的发展。我们研究了戊茶碱（PTX）是否影响人腹膜间皮细胞（HPMC）的生长和胶原合成。用酶解法从人网膜中培养羟丙甲纤维素。使用甲基四唑摄取法测定细胞增殖。流式细胞仪检测细胞周期。胶原蛋白的合成通过H-3-脯氨酸掺入抗胃蛋白酶的盐沉淀胶原蛋白来测量。酶免疫法测定前列腺素和cAMP。采用北方印迹法检测mRNA表达。我们的数据表明，PTX抑制血清刺激的HPMC的生长和胶原合成的剂量依赖性的方式。细胞周期分析显示PTX使HPMCs阻滞于G1期。PTX降低血清或转化生长因子-β（TGF-β）刺激的前胶原α 1（I）mRNA表达。PTX不改变拟南芥素的合成，但剂量依赖性地增加细胞内cAMP水平。PTX与3-异丁基-1-甲基黄嘌呤一样，可增强前列腺素E-1（PGE（1））对HPMC cAMP水平的促进作用。PTX对HPMC的抗有丝分裂和抗纤维化作用可被N-[2]-（（对溴肉桂基）氨基）乙基]-5-异喹啉磺酰胺（H-89）逆转。结论：PTX具有抑制磷酸二酯酶活性的作用。这些数据表明，PTX可能在治疗腹膜纤维化综合征中发挥作用。
Background Prevention or treatment of peritoneal fibrosing syndrome has become an important issue in patients on continuous ambulatory peritoneal dialysis (CAPD). Recent evidence has suggested that mesothelial stem cell proliferation and matrix over-production predispose the development of peritoneal fibrosis. We investigated whether pentoxifylline (PTX) affects human peritoneal mesothelial cell (HPMC) growth and collagen synthesis.Methods. HPMC was cultured from human omentum by an enzymic disaggregation method. Cell proliferation was assayed using a methyltetrazolium uptake method. Cell cycle analysis was performed by flow cytometry. Collagen synthesis was measured by H-3-proline incorporation into pepsin-resistant, salt-precipitated collagen. Prostaglandins and cAMP were determined by enzyme immunoassay. Northern blot analysis was used to determine mRNA expression.Results. Our data show that PTX inhibited serum-stimulated HPMC growth and collagen synthesis in a dose-dependent manner. Cell cycle analysis showed that PTX arrested the HPMCs in the G1 phase. PTX decreased the procollagen alpha 1 (I) mRNA expression either stimulated by serum or transforming growth factor-beta (TGF-beta). PTX did not alter prostaglandins synthesis but dose-dependently increased intracellular cAMP level. PTX, the same as 3-isobutyl-1-methylxanthine, could potentiate prostaglandin E-1 (PGE(1)) increased cAMP levels of HPMC. The antimitogenic and antifibrogenic effects of PTX on HPMC were reversed by N-[2]-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89). Therefore, the mechanism of these effects may be due to the phospodiesterase inhibitory property of PTX.Conclusions. These data suggest that PTX may have a role in treating peritoneal fibrosing syndrome.