An IL6-STAT3-MR-FGF21 Axis Mediates Heart-Liver Crosstalk after Myocardial Infarction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA796516 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17578330.fastq.gz | Fastqsanger.gz | |||
| SRR17578331.fastq.gz | Fastqsanger.gz | |||
| SRR17578332.fastq.gz | Fastqsanger.gz | |||
| SRR17578333.fastq.gz | Fastqsanger.gz | |||
| SRR17578334.fastq.gz | Fastqsanger.gz |
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Project description:The liver plays a protective role in myocardial infarction (MI). However, very little is known about the mechanisms. Here, we identify mineralocorticoid receptor (MR) as a pivotal nexus that conveys communications between the liver and the heart during MI. On one hand, hepatocyte MR deficiency and MR antagonist spironolactone both improve cardiac repair after MI through regulation on hepatic fibroblast growth factor 21 (FGF21), illustrating an MR/FGF21 axis that underlies the liver-to-heart protection against MI. On the other hand, an upstreaming acute interleukin-6 (IL6) / signal transducer and activator of transcription 3 (STAT3) pathway transmits the heart-to-liver signal to suppress MR expression after MI. Hepatocyte IL6 receptor (IL6R) deficiency and STAT3 deficiency both aggravate cardiac injury through their regulation on the MR/FGF21 axis. Therefore, we have unveiled an IL6/STAT3/MR/FGF21 signaling axis that mediates heart-liver crosstalk during MI. Targeting the signaling axis and the crosstalk may provide novel strategies to treat MI and heart failure.
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Project description:Cancer-associated cachexia (CAC) is a multifactorial, metabolic wasting syndrome that coincides with cancer malignancies of multiple entities. CAC is characterized by progressive loss of muscle mass and adipose tissue and diminishes therapy responsiveness. Here, we show that the expression of FGF21 is induced in livers of tumor-bearing mice with CAC. FGF21 deficiency promotes weight loss, exacerbates adipose tissue wasting and increases systemic inflammation, pointing towards a protective role of FGF21 in CAC. In line, IL6-mediated STAT3 activation induces FGF21 expression in hepatocytes as well as adipocytes. FGF21 promotes anabolic signaling cascades, increases cellular glucose uptake in response to IL6 exposure and counteracts cytokine-mediated glycerol release, thereby opposing adipose tissue loss in CAC. Eventually, we find that FGF21 is increased in cancer patients with clinical CAC. Together, we reveal a protective role for FGF21 in experimental CAC and identify the protein as a potential biomarker in clinical cachexia.
2025-03-06 | GSE291252 | GEO
Project description:The liver plays a protective role in myocardial infarction (MI). However, very little is known about the mechanisms. Here, we identify mineralocorticoid receptor (MR) as a pivotal nexus that conveys communications between the liver and the heart during MI. Hepatocyte MR deficiency and MR antagonist spironolactone both improve cardiac repair after MI through regulation on hepatic fibroblast growth factor 21 (FGF21), illustrating an MR/FGF21 axis that underlies the liver-to-heart protection against MI. In addition, an upstreaming acute interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway transmits the heart-to-liver signal to suppress MR expression after MI. Hepatocyte Il6 receptor deficiency and Stat3 deficiency both aggravate cardiac injury through their regulation on the MR/FGF21 axis. Therefore, we have unveiled an IL-6/STAT3/MR/FGF21 signaling axis that mediates heart-liver cross-talk during MI. Targeting the signaling axis and the cross-talk could provide new strategies to treat MI and heart failure.
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Project description:Overexpression in IL6 in MCF10A vs. WT, MCF10A.ErbB2* with/without shRNA targeting STAT3
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