Novel roles for mucin 1 in the kidney.
Novel roles for mucin 1 in the kidney.
复制标题
粘蛋白1在肾脏中的新作用。
DOI：
10.1097/mnh.0000000000000350
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发表时间：
2017-09
影响因子：
3.2
通讯作者：
Hughey RP
中科院分区：
文献类型：
--
作者：
Al-Bataineh MM;Sutton TA;Hughey RP
近年来对肾脏的研究表明，肿瘤抗原粘蛋白1（MUC 1/Muc 1）在正常和损伤的肾脏中也具有多种功能。粘蛋白1是一种跨膜粘蛋白，具有稳健的聚糖依赖性顶端靶向信号和从内体的有效再循环。最近报道TRPV 5钙通道通过半乳糖凝集素依赖性交联至粘蛋白1而稳定在细胞表面上，为调节离子通道和正常电解质平衡提供了新的机制。我们最近在小鼠中的研究表明，粘蛋白1在缺血后被诱导，稳定HIF-1α和β-catenin水平，并反式激活HIF-1和β-catenin保护通路。然而，在损伤的肾脏中延长任一途径的诱导可以从明显的完全恢复进行到慢性肾脏疾病。最近的一份报告表明，小鼠和人类缺血性损伤后粘蛋白1信号的异常激活与慢性肾脏疾病和纤维化的发展有关。MUC 1中的移码突变最近被确定为引起髓样囊性肾病1型的遗传病变，现在适当地更名为MUC 1肾病（MKD）。肾脏中粘蛋白1的研究现在揭示了细胞外粘蛋白样结构域的重要功能和通过细胞质尾的信号传导。
Recent studies in the kidney have revealed that the well-characterized tumor antigen mucin 1 (MUC1/Muc1) also has numerous functions in the normal and injured kidney. Mucin 1 is a transmembrane mucin with a robust glycan-dependent apical targeting signal and efficient recycling from endosomes. It was recently reported that the TRPV5 calcium channel is stabilized on the cell surface by galectin-dependent cross-linking to mucin 1, providing a novel mechanism for regulation of ion channels and normal electrolyte balance. Our recent studies in mice show that mucin 1 is induced after ischemia, stabilizing HIF-1α and β-catenin levels, and transactivating the HIF-1 and β-catenin protective pathways. However, prolonged induction of either pathway in the injured kidney can proceed from apparent full recovery to chronic kidney disease. A very recent report indicates that aberrant activation of mucin1 signaling after ischemic injury in mice and humans is associated with development of chronic kidney disease and fibrosis. A frame-shift mutation in MUC1 was recently identified as the genetic lesion causing Medullary Cystic Kidney Disease type 1, now appropriately renamed MUC1 Kidney Disease (MKD). Studies of mucin 1 in the kidney now reveal significant functions for the extracellular mucin-like domain and signaling through the cytoplasmic tail.