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MiR-125b enhances autophagic flux to improve septic cardiomyopathy via targeting STAT3/HMGB1.
- Source :
-
Experimental cell research [Exp Cell Res] 2021 Dec 15; Vol. 409 (2), pp. 112842. Date of Electronic Publication: 2021 Sep 24. - Publication Year :
- 2021
-
Abstract
- We explore the role of miR-125b in septic cardiomyopathy, focusing on miR-125b/STAT3/HMGB1 axis. CLP mouse model and LPS-stimulated primary rat cardiomyocytes (CMs) and H9C2 cell were used as in vivo and in vitro models of septic cardiomyopathy, respectively. qRT-PCR and western blot were performed to measure expression levels of miR-125b, STAT3, HMGB1, and autophagy-related proteins. MTT assay was employed to examine LPS toxicity. Dual luciferase activity assay and CHIP were performed to validate interactions of miR-125b/STAT3 and STAT3/HMGB1 promoter. Immunostaining was used to assess the level of autophagic flux. ROS level was measured by fluorescence assay. Heart functions were examined via intracoronary Doppler ultrasound. miR-125b was diminished while STAT3 and HMGB1 were elevated in the heart tissue following CLP surgery and in LPS-treated H9C2 cells. LPS treatment up-regulated ROS generation and suppressed autophagic flux. Overexpression of miR-125b mimics or knockdown of STAT3 or HMGB1 alleviated LPS-induced hindrance of autophagic flux and ROS production. miR-125b directly targeted STAT3 mRNA and STAT3 bound with HMGB1 promoter. Overexpression of miR-125b mitigated myocardial dysfunction induced by CLP in vivo. Hyperactivation of STAT3/HMGB1 caused by reduced miR-125b contributes to ROS generation and the hindrance of autophagic flux during septic cardiomyopathy, leading to myocardial dysfunction.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis
Cardiomyopathies etiology
Cardiomyopathies metabolism
Cardiomyopathies pathology
Cell Proliferation
HMGB1 Protein genetics
HMGB1 Protein metabolism
Mice
Rats
Rats, Sprague-Dawley
STAT3 Transcription Factor genetics
STAT3 Transcription Factor metabolism
Signal Transduction
Autophagy
Cardiomyopathies prevention & control
HMGB1 Protein antagonists & inhibitors
MicroRNAs genetics
STAT3 Transcription Factor antagonists & inhibitors
Sepsis complications
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 409
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 34563514
- Full Text :
- https://doi.org/10.1016/j.yexcr.2021.112842