Tonic repression of collagen I by the bradykinin receptor 2 in skin fibroblasts

Wong, Hui Hui; Seet, Sze Hwee; Bascom, Charles C.; Isfort, Robert J.; Bard, Frédéric

doi:10.1016/j.matbio.2023.03.004

Cited by 1 publication

(1 citation statement)

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“…TGF-β binds to TGF-β receptors and mediates downstream small mothers against decapentaplegic (SMADs)-dependent signaling cascade activation [ 10 ]. Activation of the TGF-β receptor leads to phosphorylation of the transcription factors Smad2 and Smad3 [ 11 ]. Subsequently, phosphorylated Smad2, Smad3, and cytoplasmic Smad4 form a complex and translocate into the nucleus, ultimately leading to transcriptional activation of fibrosis-related genes.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast-derived interleukin-6 exacerbates adverse cardiac remodeling after myocardial infarction

Li,

Bian

2024

Korean J Physiol Pharmacol

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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 Il6 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 Il11 promoter region and contributes to the increased expression of Il11 , 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 Il11 expression in promoting cardiac fibrosis, highlighting its potential as a therapeutic target for cardiac fibrosis.

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Section: Discussionmentioning

confidence: 99%