Evaluation of P38 MAPK Pathway as a Molecular Signature in Ulcerative Colitis
Evaluation of P38 MAPK Pathway as a Molecular Signature in Ulcerative Colitis
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P38 MAPK 通路作为溃疡性结肠炎分子特征的评估
DOI：
10.1021/pr100969w
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
Zhi, Fachao
中科院分区：
文献类型：
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作者：
Zhao, Xinmei;Kang, Bin;Zhi, Fachao
溃疡性结肠炎（UC）的早期诊断和治疗在临床上具有挑战性。为了克服这个问题，我们利用蛋白质组学中的整合策略探索了相互关联的多重信号通路来识别 UC 中的分子特征。对12例UC病例和12例正常对照的肠粘膜进行比较蛋白质组学分析。共鉴定出26个独特的差异蛋白，其中UC组中12个上调，14个下调。通过蛋白质印迹推导并验证了一个差异蛋白簇，该簇由参与 p38 丝裂原激活蛋白激酶 (MAPK) 途径的 11 个蛋白组成。此外，通过免疫组织化学对 118 个 UC 和正常样本分析了从蛋白簇中引出的三种蛋白：磷酸化 p38、MAWBP 和半乳糖凝集素 3，作为分子特征。与正常样本相比，UC 中 P-p38 表达增加，MAWBP 和/或半乳糖凝集素 3 表达下调 (p < 0.001)。该特征与 UC 疾病进展相关 (p < 0.01)，并且对 UC 风险进行高灵敏度 (94.83 +/- 2.91%) 和特异性 (98.33 +/- 1.65%) 分类。此外，P38 MAPK 通路调节巨噬细胞系中蛋白簇的表达，具体抑制剂 SB203580 的改变证明了这一点。这些结果表明 P38 MAPK 通路的分子特征可能是评估 UC 风险的潜在生物标志物。
Early diagnosis and treatment of ulcerative colitis (UC) is clinically challenging. To overcome this problem, we explored the interrelated multiplex signaling pathway to identify molecular signatures in UC by using integrated strategy in proteomics. Intestinal mucosa of 12 UC cases and 12 normal controls underwent comparative proteomic analysis. A total of 26 unique differential proteins were identified, including 12 up-regulated and 14 down-regulated in UC group. A differential protein cluster, consisting of 11 proteins involved in p38 mitogen-activated protein kinase (MAPK) pathway, was deduced and validated by Western blot. Furthermore, three proteins elicited from the protein cluster, phosphorylated p38, MAWBP and galectin-3, as a molecular signature, were analyzed by immunohistochemistry on 118 UC and normal samples. Increased expression of P-p38 and down-regulated MAWBP and/or galectin-3 were detected in UC compared to normal samples (p < 0.001). This signature correlated with disease progression of UC (p < 0.01), and classified UC risk with high sensitivity (94.83 +/- 2.91%) and specificity (98.33 +/- 1.65%). In addition, P38 MAPK pathway modulated the expression of the protein clusters in macrophage cell line as evidenced by the alteration with specific inhibitor SB203580. These results indicate that molecular signature of P38 MAPK pathway might be a potential biomarker for evaluating UC risk.