The amount of keratins matters for stress protection of the colonic epithelium.
The amount of keratins matters for stress protection of the colonic epithelium.
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DOI：
10.1371/journal.pone.0127436
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Toivola DM
中科院分区：
文献类型：
--
作者：
Asghar MN;Silvander JS;Helenius TO;Lähdeniemi IA;Alam C;Fortelius LE;Holmsten RO;Toivola DM
角蛋白（K）对于上皮应激保护是重要的，如通过诱发人类肝脏疾病和可能的炎性肠病的角蛋白突变所证明的。K8在结肠中的作用得到了K8敲除（K8−/−）小鼠中具有上皮过度增殖和异常离子转运的溃疡性结肠炎表型的支持。杂合子敲除（K8+/−）结肠表现正常，但显示部分离子转运缺陷。表征结肠表型，我们发现K8+/−结肠表达的角蛋白比K8野生型（K8+/+）少约50%，但在K8+/−和K8−/−隐窝的最顶部细胞中观察到从头K7表达。K8+/−的结肠隐窝由于上皮过度增殖而明显较长，但与K8−/−相比，在凋亡或炎症方面没有表现出缺陷。当使用葡聚糖硫酸钠模型暴露于结肠炎时，与K8+/+同窝小鼠相比，K8+/−小鼠表现出更高的疾病敏感性和延迟恢复。因此，K8+/−轻度结肠表型与角蛋白水平降低和对实验性结肠炎敏感性增加相关，表明结肠上皮中需要足够量的角蛋白来有效保护应激。
Keratins (K) are important for epithelial stress protection as evidenced by keratin mutations predisposing to human liver diseases and possibly inflammatory bowel diseases. A role for K8 in the colon is supported by the ulcerative colitis-phenotype with epithelial hyperproliferation and abnormal ion transport in K8-knockout (K8−/−) mice. The heterozygote knockout (K8+/−) colon appears normal but displays a partial ion transport-defect. Characterizing the colonic phenotype we show that K8+/− colon expresses ~50% less keratins compared to K8 wild type (K8+/+) but de novo K7 expression is observed in the top-most cells of the K8+/− and K8−/− crypts. The K8+/− colonic crypts are significantly longer due to increased epithelial hyperproliferation, but display no defects in apoptosis or inflammation in contrast to K8−/−. When exposed to colitis using the dextran sulphate sodium-model, K8+/− mice showed higher disease sensitivity and delayed recovery compared to K8+/+ littermates. Therefore, the K8+/− mild colonic phenotype correlates with decreased keratin levels and increased sensitivity to experimental colitis, suggesting that a sufficient amount of keratin is needed for efficient stress protection in the colonic epithelia.
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影响因子：
7.4
作者：
Kielland, Anders;Blom, Thomas;Carlsen, Harald
通讯作者：
Carlsen, Harald
影响因子：
3.7
作者：
Iyer SV;Dange PP;Alam H;Sawant SS;Ingle AD;Borges AM;Shirsat NV;Dalal SN;Vaidya MM
通讯作者：
Vaidya MM
DOI：
10.1126/stke.3662006pe53
发表时间：
2006-12-19
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
--
作者：
Pallari, Hanna-Mari;Eriksson, John E
通讯作者：
Eriksson, John E
影响因子：
12.6
作者：
Tao, Guo-Zhong;Strnad, Pavel;Duerr, Richard H.
通讯作者：
Duerr, Richard H.
影响因子：
4.9
作者：
Asghar, M. Nadeem;Emani, Rohini;Toivola, Diana M.
通讯作者：
Toivola, Diana M.