Mesalamine inhibits epithelial beta-catenin activation in chronic ulcerative colitis.
Mesalamine inhibits epithelial beta-catenin activation in chronic ulcerative colitis.
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DOI：
10.1053/j.gastro.2009.10.038
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发表时间：
2010-02
期刊：
影响因子：
29.4
通讯作者：
Barrett TA
中科院分区：
文献类型：
--
作者：
Brown JB;Lee G;Managlia E;Grimm GR;Dirisina R;Goretsky T;Cheresh P;Blatner NR;Khazaie K;Yang GY;Li L;Barrett TA
5-氨基水杨酸（5-ASA）是慢性溃疡性结肠炎（CUC）的主要治疗药物，它可以逆转隐窝结构变化并减少结肠炎相关癌症（CAC）。本研究探讨了5-ASA降低β-catenin相关祖细胞活化、akt磷酸化的β-cateninSer552 （P-β-catenin）和结肠炎诱导的发育不良（CID）的可能性。在轻度或“难治性”重度粘膜炎症的CUC活检中，采用免疫组化（IHC）和qRT-PCR评估5-ASA对P-β-catenin染色和功能的影响。采用免疫组化和Western blotting检测5-ASA对IL-10−/−结肠炎和CID患者上皮细胞增殖、Akt和β-catenin活化的影响。通过计算每个结肠病变的数量和长度来评估发育不良。来自IL-10−/−和人类结肠炎样本的数据显示，5-ASA降低了中上隐窝中Akt活化和P-β-catenin水平。严重炎症的CUC活检中P-β-catenin的减少表明5-ASA降低了5-ASA抗炎作用的组织中P-β-catenin的水平。在IL-10−/−小鼠中，5-ASA降低CID与抑制隐窝Akt和β-catenin信号传导一致。结果与5-ASA通过减少肠道祖细胞内β-catenin信号传导参与CAC化学预防的模型一致。
5-aminosalicylic acid (5-ASA) is a mainstay therapeutic agent in chronic ulcerative colitis (CUC) where it reverses crypt architectural changes and reduces colitis-associated cancer (CAC). The present study addressed the possibility that 5-ASA reduces β-catenin-associated progenitor cell activation, Akt-phosphorylated β-cateninSer552 (P-β-catenin), and colitis-induced dysplasia (CID). Effects of 5-ASA on P-β-catenin staining and function were assessed by IHC and qRT-PCR in biopsies of CUC in mild or “refractory” severe mucosal inflammation. Effects of 5-ASA on epithelial proliferation, and activation of Akt and β-catenin were assessed in IL-10−/− colitis and CID by IHC and Western blotting. Dysplasia was assessed by counting the number and lengths of lesions per colon. Data from IL-10−/− and human colitis samples show 5-ASA reduced Akt activation and P-β-catenin levels in the mid and upper crypt. Reductions in P-β-catenin in CUC biopsies with severe inflammation suggested that 5-ASA reduced P-β-catenin levels in tissue refractory to 5-ASA’s anti-inflammatory effects. In IL-10−/− mice, 5-ASA reduced CID concordant with inhibition of crypt Akt and β-catenin signaling. The results are consistent with the model that 5-ASA contributes to chemoprevention in CAC by reducing β-catenin signaling within intestinal progenitors.
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影响因子：
4.6
作者：
Andreu, P;Colnot, S;Romagnolo, B
通讯作者：
Romagnolo, B
DOI：
10.1016/s0006-291x(02)02983-2
发表时间：
2003-01-31
影响因子：
3.1
作者：
Farrow, B;Evers, BM
通讯作者：
Evers, BM
影响因子：
4.7
作者：
Koelink, Pim J.;Robanus-Maandag, Els C.;Verspaget, Hein W.
通讯作者：
Verspaget, Hein W.
影响因子：
4.9
作者：
Clapper, Margie L.;Gary, Monique A.;Cooper, Harry S.
通讯作者：
Cooper, Harry S.
影响因子：
5.3
作者：
Liu, Jiajian;Wang, Hong;Farmer, Stephen R.
通讯作者：
Farmer, Stephen R.