在性结肠炎中结肠上皮细胞的蛋白质差异具有表观遗传基础
Scott Jelinsky1, Isac Lee1, Mara Monetti2
1Department of Inflammation and Immunology, Pfizer, Cambridge, Massachusetts.
性结肠炎 (UC) 涉及上皮细胞的变化. 这项研究发现了UC上皮细胞表观遗传和蛋白质的差异,这表明炎症性肠病中这些变化的表观遗传调节.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 性结肠炎 (UC) 的特征是上皮功能障碍.
- 基底的细胞变化UC病理学仍然不太了解.
- 研究皮质细胞表观遗传学和UC中的蛋白质组至关重要.
研究的目的:
- 在健康对照 (HC) 和UC患者中比较结肠上皮细胞的染色质表观遗传学和蛋白质组.
- 识别可能导致UC病变的细胞差异.
- 探索调节这些差异的潜在表观遗传机制.
主要方法:
- 从HC和UC患者的结肠活检中分类活的CD326+上皮细胞.
- 分析细胞溶解物用于蛋白质组评估.
- 通过测量转化酶可访问的染色体使用测序 (ATAC-seq) 来评估开放染色体.
主要成果:
- 在炎症性UC活检中蛋白质升高包括HLA-DRA,CD74,DUOX2和利波卡林-2.
- 在炎症的UC结肠表皮中观察到降低了aquaporin 8水平.
- ATAC-seq显示了水素8和DUOX2/DUOXA2位点周围的染色质可访问性发生变化.
结论:
- 在UC患者和HC患者之间,结肠上皮细胞的蛋白质和染色质表观遗传学存在显著差异.
- 研究结果表明,特定的表观遗传机制调节了UC中的表皮细胞蛋白质组.
- 这些细胞变化可能是性结肠炎病理的基础.
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