Intestinal Alkaline Phosphatase Regulates Tight Junction Protein Levels.
Intestinal Alkaline Phosphatase Regulates Tight Junction Protein Levels.
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DOI：
10.1016/j.jamcollsurg.2015.12.006
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发表时间：
2016-06
影响因子：
5.2
通讯作者：
Hodin RA
中科院分区：
文献类型：
--
作者：
Liu W;Hu D;Huo H;Zhang W;Adiliaghdam F;Morrison S;Ramirez JM;Gul SS;Hamarneh SR;Hodin RA
肠碱性磷酸酶（IAP）在维持肠道健康和福祉方面起着关键作用。在小鼠中口服补充IAP可改善肠道屏障功能，并防止管腔促炎因子进入循环。在这项研究中，我们试图探讨IAP和紧密连接蛋白（TJP）的表达和功能之间的关系。在由IAP敲除小鼠和野生型小鼠产生的小鼠胚胎成纤维细胞（MEF）中研究IAP缺失对TJP水平的影响。通过过表达人IAP基因，在人结肠癌Caco-2和T84细胞中测定IAP对TJPs的调节。通过使用RT q-PCR和靶向特异性TJP的抗体测量紧密连接蛋白水平和定位。最后，通过体外跨孔上皮电阻（TEER）测定IAP对炎症诱导的肠通透性的影响。MEFs中肠碱性磷酸酶基因缺失导致ZO-1、ZO-2和Occludin的水平显著低于野生型对照细胞中的水平; Caco-2和T84细胞中IAP过表达导致ZO-1和ZO-2的mRNA水平增加约2倍。IAP处理改善了脂多糖诱导的Caco-2 trans-well系统的渗透性增加。此外，IAP治疗在炎症期间保留了ZO-1和Occludin蛋白的定位，并且还与改善的上皮屏障功能相关。肠碱性磷酸酶是肠粘膜通透性的主要调节剂，并且似乎至少部分地通过改善TJP水平和定位而起作用。这些数据为开发IAP作为维持肠道屏障功能的新型疗法提供了坚实的基础。
Intestinal alkaline phosphatase (IAP) plays a pivotal role in maintaining gut health and well-being. Oral supplementation with IAP in mice improves gut barrier function and prevents luminal proinflammatory factors from gaining access to the circulation. In this study, we sought to explore the relationship between IAP and tight junction protein (TJP) expression and function. The effect of IAP deletion on TJP levels was studied in mouse embryonic fibroblasts (MEFs) generated from IAP-knockout and wild type mice. Regulation of TJPs by IAP was assayed in the human colon cancer Caco-2 and T84 cells by overexpressing the human IAP gene. Tight junction protein levels and localization were measured by using RT q-PCR and antibodies targeting the specific TJPs. Finally, the effect of IAP on inflammation-induced intestinal permeability was measured by in vitro trans-well epithelial electrical resistance (TEER). Intestinal alkaline phosphatase gene deletion in MEFs resulted in significantly lower levels of ZO-1, ZO-2, and Occludin compared with levels in wild-type control cells; IAP over-expression in Caco-2 and T84 cells resulted in approximate 2-fold increases in the mRNA levels of ZO-1 and ZO-2. The IAP treatment ameliorated lipopolysaccharide-induced increased permeability in the Caco-2 trans-well system. Furthermore, IAP treatment preserved the localization of the ZO-1 and Occludin proteins during inflammation and was also associated with improved epithelial barrier function. Intestinal alkaline phosphatase is a major regulator of gut mucosal permeability and appears to work at least partly through improving TJP levels and localization. These data provide a strong foundation to develop IAP as a novel therapy to maintain gut barrier function.
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影响因子：
2.4
作者：
Bischoff SC;Barbara G;Buurman W;Ockhuizen T;Schulzke JD;Serino M;Tilg H;Watson A;Wells JM
通讯作者：
Wells JM
影响因子：
4.9
作者：
Ramasamy, Sundaram;Nguyen, Deanna D.;Eston, Michelle A.;Alam, Sayeda Nasrin;Moss, Angela K.;Ebrahimi, Farzad;Biswas, Brishti;Mostafa, Golam;Chen, Kathryn T.;Kaliannan, Kanakaraju;Yammine, Halim;Narisawa, Sonoko;Millan, Jose Luis;Warren, H. Shaw;Hohmann, Elizabeth L.;Mizoguchi, Emiko;Reinecker, Hans-Christian;Bhan, Atul K.;Snapper, Scott B.;Malo, Madhu S.;Hodin, Richard A.
通讯作者：
Hodin, Richard A.
DOI：
10.1093/gerona/glt106
发表时间：
2013-09-01
影响因子：
5.1
作者：
Lee Tran;Greenwood-Van Meerveld, Beverley
通讯作者：
Greenwood-Van Meerveld, Beverley
DOI：
10.1073/pnas.1220180110
发表时间：
2013-04-23
影响因子：
11.1
作者：
Kaliannan, Kanakaraju;Hamarneh, Sulaiman R.;Hodin, Richard A.
通讯作者：
Hodin, Richard A.
影响因子：
6
作者：
Guo, Shuhong;Al-Sadi, Rana;Ma, Thomas Y.
通讯作者：
Ma, Thomas Y.