The role of CDX2 in renal tubular lesions during diabetic kidney disease.
The role of CDX2 in renal tubular lesions during diabetic kidney disease.
复制标题
DOI：
10.18632/aging.202537
复制
发表时间：
2021-02-17
期刊：
影响因子：
--
通讯作者：
Guo B
中科院分区：
文献类型：
--
作者：
Liu H;Yan R;Liang L;Zhang H;Xiang J;Liu L;Zhang X;Mao Y;Peng W;Xiao Y;Zhang F;Zhou Y;Shi M;Wang Y;Guo B
糖尿病肾病（DKD）中，肾小管是引起肾损伤的各种因素的易感目标，肾小管病变的程度与肾功能密切相关。肾小管上皮细胞（RTECs）的异常分化和细胞连接蛋白的缺失在DKD发病机制中是重要的。尾型同源框转录因子2（CDX 2）是维持肠上皮细胞正常增殖和分化的关键核转录因子。本研究旨在评估CDX 2对DKD中RTECs分化和细胞连接蛋白的影响。结果表明，CDX 2主要定位于肾小管，并在各种DKD模型中下调。CDX 2可上调E-cadherin表达，抑制部分上皮-间质转化（EMT），从而减轻高糖血症对RTECs的损伤。在NRK-52 E细胞中，囊性纤维化跨膜传导调节因子（CFTR）受CDX 2调节，并且CFTR通过与Dvl 2结合来干扰β-catenin活化，Dvl 2是Wnt/β-catenin信号传导的重要组分。CFTR敲除消除了CDX 2对Wnt/β-catenin信号传导的抑制作用，从而上调了细胞连接蛋白并抑制了RTEC中的部分EMT。总之，CDX 2可以通过增加CFTR量以抑制Wnt/β-连环蛋白信号传导途径来改善DKD期间的肾小管病变。
Renal tubules are vulnerable targets of various factors causing kidney injury in diabetic kidney disease (DKD), and the degree of tubular lesions is closely related to renal function. Abnormal renal tubular epithelial cells (RTECs) differentiation and depletion of cell junction proteins are important in DKD pathogenesis. Caudal-type homeobox transcription factor 2 (CDX2), represents a key nuclear transcription factor that maintains normal proliferation and differentiation of the intestinal epithelium. The present study aimed to evaluate the effects of CDX2 on RTECs differentiation and cell junction proteins in DKD. The results demonstrated that CDX2 was mainly localized in renal tubules, and downregulated in various DKD models. CDX2 upregulated E-cadherin and suppressed partial epithelial-mesenchymal transition (EMT), which can alleviate hyperglycemia-associated RTECs injury. Cystic fibrosis transmembrane conductance regulator (CFTR) was regulated by CDX2 in NRK-52E cells, and CFTR interfered with β-catenin activation by binding to Dvl2, which is an essential component of Wnt/β-catenin signaling. CFTR knockdown abolished the suppressive effects of CDX2 on Wnt/β-catenin signaling, thereby upregulating cell junction proteins and inhibiting partial EMT in RTECs. In summary, CDX2 can improve renal tubular lesions during DKD by increasing CFTR amounts to suppress the Wnt/β-catenin signaling pathway.
登录
查看更多内容
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Sancho, Ana;Li, SiDe;Walsh, Martin J.
通讯作者：
Walsh, Martin J.
影响因子：
4.1
作者：
Kerschner, Jenny L.;Harris, Ann
通讯作者：
Harris, Ann
影响因子：
9.7
作者：
Gnemmi, Viviane;Bouillez, Audrey;Perrais, Michael
通讯作者：
Perrais, Michael
影响因子：
12.4
作者：
Sun, Xiaofei;Yang, Qiyuan;Zhu, Mei-Jun
通讯作者：
Zhu, Mei-Jun