Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis
Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis
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DOI：
10.1016/s0090-4295(03)00005-0
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发表时间：
2003-06-01
期刊：
影响因子：
2.1
通讯作者：
Chai, TC
中科院分区：
文献类型：
--
作者：
Keay, S;Zhang, CO;Chai, TC
目标.确定间质性膀胱炎（IC）患者的膀胱上皮细胞是否在体外显示固有的增殖率降低，并比较未经治疗的IC和正常膀胱细胞与用IC患者尿液中发现的纯化抗增殖因子（APF）治疗的正常细胞的生长率。从4例IC患者和2例无症状对照的膀胱活检组织中制备上皮细胞外植体。通过台盼蓝阴性细胞的连续计数来确定细胞增殖。APF和模拟APF纯化色谱法，并通过H-3-胸苷掺入原代正常膀胱上皮细胞的活性测定。用酶联免疫吸附法测定肝素结合表皮生长因子样生长因子和表皮生长因子。血清饥饿后第2天，IC患者的膀胱上皮细胞增殖显著低于对照细胞（P = 0.02）。在APF处理的对照细胞中观察到类似的增殖抑制率; APF诱导的肝素结合表皮生长因子样生长因子（而非表皮生长因子）的变化与细胞生长率的变化相关。IC患者膀胱上皮细胞在无血清培养基中的增殖率明显低于对照细胞，表明IC细胞增殖的内在异常。这种异常可能是由APF引起的，APF诱导肝素结合表皮生长因子样生长因子的产生和正常膀胱上皮细胞增殖的可逆性抑制。
Objectives. To determine whether explanted bladder epithelial cells from patients with interstitial cystitis (IC) display intrinsically decreased rates of proliferation in vitro, and to compare the growth rates of untreated IC and normal bladder cells with the rates of normal cells treated with a purified antiproliferative factor (APF) at levels found in urine from patients with IC.Methods. Epithelial cell explants were prepared from the bladder biopsies of 4 patients with IC and 2 asymptornatic controls. Cell proliferation was determined by serial counting of trypan blue-negative cells. APF and mock APF were purified chromatographically, and activity was determined by H-3-thymidine incorporation into primary normal bladder epithelial cells. Heparin-binding epidermal growth factor-like growth factor and epidermal growth factor were measured by enzyme-linked immunosorbent assay.Results. Bladder epithelial cells from patients with IC proliferated significantly less than did control cells by day 2 after serum starvation (P = 0.02). Similar inhibition of the proliferation rate was seen in control cells treated with APF; APF-induced changes in heparin-binding epidermal growth factor-like growth factor, but not epidermal growth factor, production by cells were associated with changes in growth rates.Conclusions. The proliferation rate of explanted bladder epithelial cells from patients with IC in serum-free medium was significantly less than that of control cells, indicating an intrinsic abnormality in IC cell proliferation. This abnormality may be caused by APF, which induces reversible inhibition of heparin-binding epidermal growth factor-like growth factor production and normal bladder epithelial cell proliferation.