Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
We previously demonstrated receptor for advanced glycation end products (RAGE) was required for β-catenin stabilization in a toluene diisocyanate (TDI)-induced asthma model, suggesting it plays an important role in TDI-induced airway inflammation. The aim of this study was to examine whether RAGE mediates β-catenin stabilization via activation of the Src/p-Cav-1 axis in TDI-induced asthma model. To generate a chemical-induced asthma model, male BALB/c mice were sensitized and challenged with TDI. Before each challenge, FPS-ZM1 (RAGE inhibitor) and PP2 (Src inhibitor) was given via intraperitoneal injection. In the TDI-exposed mice, airway reactivity, airway inflammation, goblet cell metaplasia, and the release of Th2 cytokines and IgE increased significantly. The level of membrane β-catenin decreased but was increased in the cytoplasm. Increased expression of RAGE, p-Src, and p-Cav-1 was also detected in TDI-exposed lungs. However, all these changes were inhibited by FPS-ZM1 and PP2. In TDI-HSA stimulated human airway epithelial (16HBE) cells, the expression of p-Src and p-Cav-1, and the abnormal distribution of β-catenin were significantly increased, and then inhibited in RAGE knockdown cells. Similarly, PP2 or non-phosphorylatable Cav-1 mutant (Y14F-Cav-1) treated 16HBE cells had the same effect on the distribution of β-catenin. In addition, blockage of RAGE signaling and phosphorylation of Cav-1 eliminated the translocation of β-catenin from cytomembrane to cytoplasm. Our results showed that RAGE modulates β-catenin aberrant distribution via activation of Src/p-Cav-1 in a chemical-induced asthma model.
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Source |
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http://dx.doi.org/10.1016/j.toxlet.2018.09.010 | DOI Listing |
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