M2b Macrophages Regulate Cardiac Fibroblast Activation and Alleviate Cardiac Fibrosis After Reperfusion Injury.

Abstract

BACKGROUND:

Macrophages play an important role in the development of cardiac fibrosis. However, the roles of different macrophage subtypes in cardiac fibroblast (CF) activation and cardiac fibrosis are unknown.Methods and Results:Bone marrow-derived macrophages (BMDMs) were treated with different stimuli to induce differentiation into M1, M2a, M2b, and M2c macrophage subtypes. CFs were co-cultured with different subtypes of macrophages or cultured with macrophage supernatants. Results revealed that M2b macrophages significantly suppressed the proliferation and migration of CFs, the expression of fibrosis-related proteins (collagen I [COL-1] and α-smooth muscle actin [α-SMA]), and differentiation into cardiac myofibroblasts (MFs). The opposite effects were observed with M2a macrophages. A rat model of cardiac ischemia/reperfusion (I/R) injury was used to determine the effect of M2b macrophages transplantation. After cardiac I/R injury, transplantation of M2b macrophages improved cardiac function and reduced cardiac fibrosis. The effect of macrophage subtypes on p-ERK, ERK, p-p38, and p38 phosphorylation was examined by Western blotting. The results showed that M2b macrophages significantly inhibited the mitogen-activated protein kinase (MAPK) signaling pathway.

CONCLUSIONS:

These study results demonstrate for the first time that different subtypes of macrophages have different roles in regulating CF activation. M2b macrophages inhibit CF activation, and thus can be considered anti-fibrotic macrophages. M2a macrophages promote CF activation, and thus are pro-fibrotic macrophages.

• Authors: Yuan Yue, Suiqing Huang, Lexun Wang, Zixuan Wu, Mengya Liang, Huayang Li, Linhua Lv, Wei Li, Zhongkai Wu
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 84 Issue 4 Pg. 626-635 (03 25 2020) ISSN: 1347-4820 [Electronic] Japan
• PMID: 32161201 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Actins
• Collagen Type I
• smooth muscle actin, rat
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Actins (metabolism)
• Animals
• Cell Communication
• Cell Differentiation
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Coculture Techniques
• Collagen Type I (metabolism)
• Disease Models, Animal
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibroblasts (metabolism, pathology)
• Fibrosis
• Macrophages (metabolism, pathology)
• Male
• Myocardial Infarction (metabolism, pathology, prevention & control)
• Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
• Myocardium (metabolism, pathology)
• Phenotype
• Phosphorylation
• Rats, Sprague-Dawley
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases (metabolism)