Defective CFTR leads to aberrant beta-catenin activation and kidney fibrosis
Publication in refereed journal


Times Cited
Altmetrics Information
.

Other information
AbstractCystic fibrosis transmembrane conductance regulator (CFTR), known as a cAMP-activated Cl-channel, is widely expressed at the apical membrane of epithelial cells in a wide variety of tissues. Of note, despite the abundant expression of CFTR in mammalian kidney, the role of CFTR in kidney disease development is unclear. Here, we report that CFTR expression is downregulated in the UUO (unilateral ureteral obstruction)-induced kidney fibrosis mouse model and human fibrotic kidneys. Dysfunction or downregulation of CFTR in renal epithelial cells leads to alteration of genes involved in Epithelial-Mesenchymal Transition (EMT) and kidney fibrosis. In addition, dysregulation of CFTR activates canonical Wnt/beta-catenin signaling pathways, whereas the beta-catenin inhibitor reverses the effects of CFTR downregulation on EMT marker. More interestingly, CFTR interacts with Dishevelled 2 (Dvl2), a key component of Wnt signaling, thereby suppressing the activation of beta-catenin. Compared to wild type, deltaF508 mice with UUO treatment exhibit significantly higher beta-catenin activity with aggregated kidney fibrogenesis, which is reduced by forced overexpression of CFTR. Taken together, our study reveals a novel mechanism by which CFTR regulates Wnt/beta-catenin signaling pertinent to progression of kidney fibrosis and indicates a potential treatment target.
All Author(s) ListJie Ting ZHANG, Yan WANG, Jun Jiang CHEN, Xiao Hu ZHANG, Jian Da DONG, Lai Ling TSANG, Xiao Ru HUANG, Zhiming CAI, Hui Yao LAN, Xiao Hua JIANG, Hsiao Chang CHAN
Journal nameScientific Reports
Year2017
Month7
Day12
Volume Number7
Issue Number1
PublisherNATURE PUBLISHING GROUP
Pages5233
ISSN2045-2322
eISSN2045-2322
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesMultidisciplinary Sciences;Science & Technology - Other Topics

Last updated on 2020-25-05 at 00:04