| Title: |
M1 macrophage-derived exosomes inhibit cardiomyocyte proliferation through delivering miR-155 |
| Authors: |
Xiaoqing He, Shan Liu, Zhanyu Zhang, Qirui Liu, Juan Dong, Zhifeng Lin, Junhao Chen, Lihuan Li, Weihua Liu, Shaojun Liu, Shiming Liu |
| Source: |
BMC Cardiovascular Disorders, Vol 24, Iss 1, Pp 1-11 (2024) |
| Publisher Information: |
BMC, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Diseases of the circulatory (Cardiovascular) system |
| Subject Terms: |
M1 macrophage, Exosomes, Mir-155, Myocardial infarction, Cardiomyocyte proliferation, Diseases of the circulatory (Cardiovascular) system, RC666-701 |
| More Details: |
Abstract Background M1 macrophages are closely associated with cardiac injury after myocardial infarction (MI). Increasing evidence shows that exosomes play a key role in pathophysiological regulation after MI, but the role of M1 macrophage-derived exosomes (M1-Exos) in myocardial regeneration remains unclear. In this study, we explored the impact of M1 macrophage-derived exosomes on cardiomyocytes regeneration in vitro and in vivo. Methods M0 macrophages were induced to differentiate into M1 macrophages with GM-CSF (50 ng/mL) and IFN-γ (20 ng/mL). Then M1-Exos were isolated and co-incubated with cardiomyocytes. Cardiomyocyte proliferation was detected by pH3 or ki67 staining. Quantitative real-time PCR (qPCR) was used to test the level of miR-155 in macrophages, macrophage-derived exosomes and exosome-treated cardiomyocytes. MI model was constructed and LV-miR-155 was injected around the infarct area, the proliferation of cardiomyocytes was counted by pH3 or ki67 staining. The downstream gene and pathway of miR-155 were predicted and verified by dual-luciferase reporter gene assay, qPCR and immunoblotting analysis. IL-6 (50 ng/mL) was added to cardiomyocytes transfected with miR-155 mimics, and the proliferation of cardiomyocytes was calculated by immunofluorescence. The protein expressions of IL-6R, p-JAK2 and p-STAT3 were detected by Western blot. Results The results showed that M1-Exos suppressed cardiomyocytes proliferation. Meanwhile, miR-155 was highly expressed in M1-Exos and transferred to cardiomyocytes. miR-155 inhibited the proliferation of cardiomyocytes and antagonized the pro-proliferation effect of interleukin 6 (IL-6). Furthermore, miR-155 targeted gene IL-6 receptor (IL-6R) and inhibited the Janus kinase 2(JAK)/Signal transducer and activator of transcription (STAT3) signaling pathway. Conclusion M1-Exos inhibited cardiomyocyte proliferation by delivering miR-155 and inhibiting the IL-6R/JAK/STAT3 signaling pathway. This study provided new insight and potential treatment strategy for the regulation of myocardial regeneration and cardiac repair by macrophages. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1471-2261 |
| Relation: |
https://doaj.org/toc/1471-2261 |
| DOI: |
10.1186/s12872-024-03893-0 |
| Access URL: |
https://doaj.org/article/2290bb38dc76400ba2fc480466a36995 |
| Accession Number: |
edsdoj.2290bb38dc76400ba2fc480466a36995 |
| Database: |
Directory of Open Access Journals |
