Fibroblast-derived interleukin-6 exacerbates adverse cardiac remodeling after myocardial infarction
Myocardial infarction is one of the leading causes of mortality globally. Currently, the pleiotropic inflammatory cytokine interleukin-6 (IL-6) is considered to be intimately related to the severity of myocardial injury during myocardial infarction. Interventions targeting IL-6 are a promising thera...
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Published in | The Korean journal of physiology & pharmacology Vol. 28; no. 3; pp. 285 - 294 |
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Main Authors | , |
Format | Journal Article |
Language | English Korean |
Published |
Korea (South)
The Korean Physiological Society and The Korean Society of Pharmacology
01.05.2024
대한약리학회 |
Subjects | |
Online Access | Get full text |
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Summary: | Myocardial infarction is one of the leading causes of mortality globally. Currently, the pleiotropic inflammatory cytokine interleukin-6 (IL-6) is considered to be intimately related to the severity of myocardial injury during myocardial infarction. Interventions targeting IL-6 are a promising therapeutic option for myocardial infarction, but the underlying molecular mechanisms are not well understood. Here, we report the novel role of IL-6 in regulating adverse cardiac remodeling mediated by fibroblasts in a mouse model of myocardial infarction. It was found that the elevated expression of IL-6 in myocardium and cardiac fibroblasts was observed after myocardial infarction. Further, fibroblast-specific knockdown of
significantly attenuated cardiac fibrosis and adverse cardiac remodeling and preserved cardiac function induced by myocardial infarction. Mechanistically, the role of Il6 contributing to cardiac fibrosis depends on signal transduction and activation of transcription (STAT)3 signaling activation. Additionally, Stat3 binds to the
promoter region and contributes to the increased expression of
, which exacerbates cardiac fibrosis. In conclusion, these results suggest a novel role for IL-6 derived from fibroblasts in mediating Stat3 activation and substantially augmented
expression in promoting cardiac fibrosis, highlighting its potential as a therapeutic target for cardiac fibrosis. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 KISTI1.1003/JNL.JAKO202413757621762 Author contributions: H.L. performed the experiments, and collected and analyzed the data. Y.B. conceived and designed the experiments. |
ISSN: | 1226-4512 2093-3827 |
DOI: | 10.4196/kjpp.2024.28.3.285 |