活性溃疡性结肠炎中结肠维生素 D 受体表达与疾病活动度呈负相关，与 jumonji 结构域包含蛋白 3 相关。
Colonic vitamin D receptor expression is inversely associated with disease activity and jumonji domain-containing 3 in active ulcerative colitis.
机构信息
Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China.
Department of Pathogen Biology, Anhui Medical University, Hefei 230032, Anhui Province, China.
出版信息
World J Gastroenterol. 2020 Dec 14;26(46):7352-7366. doi: 10.3748/wjg.v26.i46.7352.
BACKGROUND
The expression of jumonji domain-containing 3 (Jmjd3) and trimethylated H3 lysine 27 (H3K27me3) in active ulcerative colitis (UC) and the correlation between vitamin D receptor (VDR) and the Jmjd3 pathway are unknown.
AIM
To study the relationship between VDR, Jmjd3 and H3K27me3 in patients with active UC.
METHODS
One hundred patients with active UC and 56 healthy controls were enrolled in this study. The patients with active UC were divided into groups according to mild ( = 29), moderate ( = 32) and severe ( = 29) disease activity based on the modified Mayo score. Vitamin D levels were measured by radioimmunoassay. Colonic mucosal tissues from UC patients and controls were collected by colonoscopy. The expression of VDR, Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining.
RESULTS
Patients with active UC had lower levels of serum vitamin D (13.7 ± 2.8 ng/mL, < 0.001) than the controls (16.2 ± 2.5 ng/mL). In the UC cohort, serum vitamin D level was negatively correlated with disease activity ( = -0.323, = 0.001). VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues ( < 0.001) and negatively correlated with disease activity ( = -0.868, < 0.001). Similar results for VDR expression were noted in the most serious lesion (defined as UC diseased) and 20 cm proximal to the anus (defined as UC normal) ( < 0.05). Simultaneously, Jmjd3 expression significantly increased in UC patients ( < 0.001), but no difference was found between the different sites in UC patients. H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues ( < 0.001), but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients ( < 0.05). Jmjd3 Level was negatively correlated with the level of VDR ( = -0.342, = 0.002) and H3K27me3 ( = -0.341, = 0.002), while VDR level was positively correlated with H3K27me3 ( = 0.473, < 0.001).
CONCLUSION
Serum vitamin D and VDR were inversely correlated with disease activity in active UC. Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.
背景
在活动期溃疡性结肠炎（UC）中， jumonji 结构域包含 3（Jmjd3）和三甲基化 H3 赖氨酸 27（H3K27me3）的表达以及维生素 D 受体（VDR）与 Jmjd3 途径之间的相关性尚不清楚。
目的
研究活动期 UC 患者中 VDR、Jmjd3 和 H3K27me3 之间的关系。
方法
本研究纳入了 100 例活动期 UC 患者和 56 名健康对照者。根据改良 Mayo 评分，将活动期 UC 患者分为轻度（ = 29）、中度（ = 32）和重度（ = 29）疾病活动组。采用放射免疫法测定血清维生素 D 水平。通过结肠镜收集 UC 患者和对照者的结肠黏膜组织。采用免疫组织化学染色法检测肠黏膜中 VDR、Jmjd3 和 H3K27me3 的表达。
结果
与对照组（16.2 ± 2.5ng/ml）相比，活动期 UC 患者的血清维生素 D 水平较低（13.7 ± 2.8ng/ml， < 0.001）。在 UC 队列中，血清维生素 D 水平与疾病活动呈负相关（ = -0.323， = 0.001）。与正常组织相比，UC 患者的黏膜中 VDR 表达减少（ < 0.001），且与疾病活动呈负相关（ = -0.868， < 0.001）。在最严重的病变（定义为 UC 病变）和距肛门 20cm 处（定义为 UC 正常），也观察到类似的 VDR 表达结果（ < 0.05）。同时，UC 患者的 Jmjd3 表达显著增加（ < 0.001），但在 UC 患者不同部位之间无差异。与正常组织相比，UC 患者的 H3K27me3 表达显著下调（ < 0.001），但在轻度疾病活动组与中度疾病活动组 UC 患者相比，H3K27me3 表达上调（ < 0.05）。Jmjd3 水平与 VDR（ = -0.342， = 0.002）和 H3K27me3（ = -0.341， = 0.002）水平呈负相关，而 VDR 水平与 H3K27me3 水平呈正相关（ = 0.473， < 0.001）。
结论
在活动期 UC 中，血清维生素 D 和 VDR 与疾病活动呈负相关。Jmjd3 在活动期 UC 患者的结肠黏膜中表达增加，与 VDR 和 H3K27me3 水平呈负相关。
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