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Message: fopen(/var/lib/php/sessions/ci_sessionq0ui1pi9paneslrhb4c5l7g00k4rn6u3): Failed to open stream: No space left on device
Filename: drivers/Session_files_driver.php
Line Number: 177
Backtrace:
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)
Filename: Session/Session.php
Line Number: 137
Backtrace:
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Cardiac fibrosis is a common pathological manifestation in multiple cardiovascular diseases and often results in myocardial stiffness and cardiac dysfunctions. LncRNA (long noncoding RNA) participates in a number of pathophysiological processes. However, its role in cardiac fibrosis remains unclear. The purpose of this study was to investigate the role and molecular mechanism of MetBil in regulating cardiac fibrosis. Our data showed that METTL3 binding lncRNA (MetBil) was significantly increased both in fibrotic tissue following myocardial infarction (MI) in mice and in cardiac fibroblasts (CFs) exposed to TGF-β1 (20 ng/mL) or 20% FBS. Overexpression of MetBil augmented collagen deposition, CF proliferation and activation while silencing MetBil exhibited the opposite effects. Importantly, heterozygous knockout of MetBil alleviated cardiac fibrosis and improved cardiac function after MI. RNA pull-down and RNA-binding protein immunoprecipitation assay showed that METTL3 is a direct downstream target of MetBil; consistently, MetBil and METTL3 were co-localized in both the nucleus and cytoplasm of CFs. Interestingly, MetBil regulated METTL3 expression at protein level, but not mRNA level, in ubiquitin-proteasome pathway. Enforced expression of METTL3 canceled the antifibrotic effects of silencing MetBil reflected by increased collagen production, CF proliferation and activation. Most notably, the m6A-modified fibrosis-regulated genes mediated by METTL3 are profoundly involved in the regulation of MetBil in the cardiac fibrosis following MI. Our study reveals that MetBil as a novel regulator of fibrosis promotes cardiac fibrosis via interacting with METTL3 and regulating the expression of the methylated fibrosis-associated genes, providing a new intervening target for fibrosis-associated cardiac diseases.
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Source |
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http://dx.doi.org/10.1096/fj.202201734R | DOI Listing |
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