Related Experiment Video
Updated: Jun 29, 2026
Visualization of Vascular Ca2+ Signaling Triggered by Paracrine Derived ROS
Published on: December 21, 2011
Snhg14/miR-181a-5p axis-mediated "M1" macrophages aggravate LPS-induced myocardial cell injury
Chenglong Bi1, Dejin Wang1, Bin Hao2
1Department of Cardiology, Shandong University Zibo Central Hospital, Zibo, 255000, Shandong, China.
Abstract:
An increasing number of studies have suggested that macrophages participate in sepsis-induced myocardial injury. Our study highlights the function and mechanism of the lncRNA Snhg14 in "M1" polarized macrophage-mediated myocardial cell damage. Lipopolysaccharide (LPS) was used to treat H9c2 cells to construct an in vitro myocardial injury model. M1 and M2 polarization of RAW264.7 cells were induced and the exosomes were obtained from the supernatant through ultracentrifugation. Moreover, cecal ligation and puncture (CLP) surgery was implemented to establish a mouse sepsis-induced myocardial injury model, and Snhg14 was knocked down with sh-Snhg14. The results showed that the conditioned medium (CM) and the exosomes (Exo) of M1 macrophages substantially augmented LPS-induced apoptosis and oxidative stress in myocardial cells. Notably, M1-CM and M1-Exo contributed to nearly 50 % of myocardial cell viability decline. Snhg14 was highly expressed in M1 macrophages and exosomes derived from M1-MΦ (M1-Exo). Snhg14 overexpression aggravated myocardial cell damage and increased 10 to 50 times expression of proinflammatory cytokines in MΦ. Snhg14 knockdown reversed M1-Exo-mediated myocardial cell damage and inhibited the production of proinflammatory cytokines (50 %-75 % decline) of MΦ. Moreover, Snhg14 targeted and inhibited miR-181a-5p expression. miR-181a-5p upregulation partly reversed Snhg4 overexpression-mediated myocardial cell damage and MΦ activation. In vivo, sh-Snhg14 dramatically ameliorated cardiac damage in septic mice by enhancing miR-181a-5p and inhibiting the HMGB1/NF-κB pathway. In conclusion, "M1" macrophage-derived exosomal Snhg14 aggravates myocardial cell damage by modulating the miR-181a-5p/HMGB1/NF-κB pathway.
Insights
M1 macrophage-derived exosomes carrying Snhg14 long non-coding RNA worsen sepsis-induced heart damage. Knocking down Snhg14 protects the heart by targeting miR-181a-5p and inhibiting the HMGB1/NF-κB pathway.
Area of Science:
- Cardiovascular Biology
- Immunology
- Molecular Biology
Background:
- Sepsis-induced myocardial injury is a critical complication.
- Macrophages, particularly M1 polarized, play a significant role in this injury.
- The specific mechanisms involving long non-coding RNAs (lncRNAs) in this process require further elucidation.
Purpose of the Study:
- To investigate the role and mechanism of lncRNA Snhg14 in M1 macrophage-mediated myocardial cell damage during sepsis.
- To explore the regulatory pathway involving Snhg14, miR-181a-5p, and the HMGB1/NF-κB signaling pathway.
Main Methods:
- Established in vitro (LPS-treated H9c2 cells) and in vivo (cecal ligation and puncture-induced sepsis in mice) models of myocardial injury.
- Induced M1 and M2 polarization in RAW264.7 cells and isolated exosomes.
- Utilized Snhg14 knockdown (sh-Snhg14) and miR-181a-5p upregulation strategies.
- Assessed myocardial cell apoptosis, oxidative stress, cytokine expression, and cardiac damage.
Main Results:
- M1 macrophage-derived conditioned medium and exosomes exacerbated LPS-induced myocardial cell apoptosis and oxidative stress.
- Snhg14 was highly expressed in M1 macrophages and their exosomes, and its overexpression aggravated myocardial damage and inflammation.
- Snhg14 knockdown reversed M1 exosome-mediated damage and inhibited pro-inflammatory cytokine production.
- Snhg14 directly targeted and inhibited miR-181a-5p, and miR-181a-5p upregulation partially reversed Snhg14-induced damage.
- In vivo, Snhg14 knockdown ameliorated cardiac damage by enhancing miR-181a-5p and inhibiting the HMGB1/NF-κB pathway.
Conclusions:
- Exosomal Snhg14 derived from M1 macrophages aggravates sepsis-induced myocardial injury.
- The mechanism involves Snhg14 modulating the miR-181a-5p/HMGB1/NF-κB pathway.
- Targeting Snhg14 may represent a therapeutic strategy for sepsis-induced heart damage.
