The effect of epigenetic therapy on congenital neurogenic bladders--a pilot study.
The effect of epigenetic therapy on congenital neurogenic bladders--a pilot study.
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DOI：
10.1016/j.urology.2009.11.022
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发表时间：
2010-04
期刊：
影响因子：
2.1
通讯作者：
Atala A
中科院分区：
文献类型：
--
作者：
Hodges SJ;Yoo JJ;Mishra N;Atala A
证明来自神经源性膀胱的人类平滑肌细胞在体外比来自正常膀胱的平滑肌细胞产生更多的胶原蛋白，并且表观遗传治疗可能使这种增加的胶原蛋白产生正常化。将正常膀胱（n = 3）和神经源性膀胱（n = 3）的人平滑肌细胞培养在正常培养基中，并在不同浓度的组蛋白去乙酰化酶抑制剂曲古斯汀A、丙戊酸和DNA甲基化抑制剂5-氮杂胞苷（5-aza）中培养。不同剂量药物暴露后，采用实时定量逆转录-聚合酶链反应检测I型和III型胶原基因表达。台盼蓝法测定细胞活力。在正常条件下，神经源性膀胱平滑肌细胞释放的胶原蛋白明显多于正常膀胱细胞（在对照培养基中平均4.1 μg/mL vs 1.8 μg/mL）。50 ng/mL曲古霉素A可使神经源性膀胱细胞中的胶原蛋白水平降至接近正常水平（2.1 μg/mL）。此外，与对照组相比，丙戊酸处理降低了I型和III型胶原基因的表达，在300 mg/mL时效果最大。这些处理对细胞活力几乎没有影响。组蛋白去乙酰化酶抑制剂可减少体外神经源性膀胱平滑肌细胞的胶原生成。这些药物可能是有效预防膀胱纤维化的一种方法。
To demonstrate that human smooth muscle cells derived from neurogenic bladders produce more collagen in vitro than smooth muscle cells derived from normal bladders, and that epigenetic therapy may normalize this increased collagen production. Human smooth muscle cells from normal (n = 3) and neurogenic bladders (n = 3) were cultured in normal culture media and at different concentrations of the histone deacetylase inhibitors trichostatin A, valproic acid, and the DNA methylation inhibitor 5-azacytidine (5-aza). Collagen type I and III gene expression was measured using real-time quantitative reverse transcription-polymerase chain reaction after varying doses of drug exposure. Cell viability was measured using trypan blue. The smooth muscle cells from neurogenic bladders released significantly more collagen than the normal bladder cells (mean 4.1 vs 1.8 μg/mL in control media) when grown in normal conditions. Treatment with trichostatin A at 50 ng/mL decreased the collagen level in cells from neurogenic bladders to almost normal levels (2.1 μg/mL). In addition, valproic acid treatment decreased collagen types I and III gene expression relative to controls, with maximal effect at 300 mg/mL. These treatments had little effect on cell viability. Histone deacetylase inhibitors decreased collagen production of smooth muscle cells from neurogenic bladders in vitro. These agents may be a means of effectively preventing bladder fibrosis in patients with this condition.
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