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: 1034
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016
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
Melatonin (Mel) has been documented to modulate epithelial-mesenchymal transition (EMT) in cellular systems. The interstitial transformation of renal tubular epithelial cells constitutes a key pathogenic mechanism underlying renal fibrosis. This study aims to elucidate the role of Mel in the EMT process of renal tubular epithelial cells. A rat model of unilateral ureteral obstruction (UUO) was developed through unilateral ureteral ligation, followed by treatment with Mel (5, 10, and 20 mg/kg). Subsequent analyses included histopathological examination, measurement of creatinine and blood urea nitrogen levels, immunofluorescence analysis of fibronectin (FN), and immunohistochemical analysis of alpha-smooth muscle actin (α-SMA). Transforming growth factor-beta 1 (TGF-β1) initiates a fibrotic response in NRK-52E cells, which is subsequently treated with Mel (0. 1, 1, and 10 μmol/L). Evaluates cell viability, migration, and the expression of EMT related proteins, including FN, α-SMA, collagenase I, and E-cadherin. To validate the regulatory interaction between miR-153-3p and Forkhead transcription factor o subfamily member 3A (FOXO3A), cells are transfected with miR-153-3p mimics or siRNA targeting FOXO3A (si-FOXO3A). In results Mel exhibits a dose-dependent capacity to ameliorate renal injury and rectify glomerular structural abnormalities in UUO rat models. In comparison to UUO model rats, melatonin significantly reduced the expression levels of FN and α-SMA. In vitro studies demonstrated that Mel inhibited the activity and migratory behavior of cells, as well as the protein expression levels of FN, α-SMA, and collagenase I in NRK-52E cells. Relative to the control group, UUO rats and TGF-β1-induced NRK-52E cells exhibited elevated expression of miR-153-3p and reduced FOXO3A. In vitro models further revealed that upregulation of miR-153-3p or downregulation of FOXO3A can negate the protective effects of Melatonin on TGF-β1-induced EMT. Concluding, Mel inhibits miR-153-3p, thereby promoting the transcription of FOXO3A in UUO rats, which alleviates renal injury and attenuates TGF-1-induced EMT in cells.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.26402/jpp.2024.5.02 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!