scholarly journals IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE2-mediated M2 macrophage polarization

Theranostics ◽  
2020 ◽  
Vol 10 (17) ◽  
pp. 7697-7709
Author(s):  
Xiaocang Cao ◽  
Liyun Duan ◽  
Huixing Hou ◽  
Yue Liu ◽  
Shang Chen ◽  
...  
2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zeng-Ping Kang ◽  
Meng-Xue Wang ◽  
Tian-Tian Wu ◽  
Duan-Yong Liu ◽  
Hai-Yan Wang ◽  
...  

Curcumin has shown good efficacy in mice with experimental colitis and in patients with ulcerative colitis, but the mechanism of action through the regulation of M1/M2 macrophage polarization has not been elaborated. The ulcerative colitis was modeled by dextran sulfate sodium; colitis mice were orally administrated with curcumin (10 mg/kg/day) or 5-ASA (300 mg/kg/day) for 14 consecutive days. After curcumin treatment, the body weight, colon weight and length, colonic weight index, and histopathological damage in colitis mice were effectively improved. The concentrations of proinflammatory cytokines IL-1β, IL-6, and CCL-2 in the colonic tissues of colitis mice decreased significantly, while anti-inflammatory cytokines IL-33 and IL-10 increased significantly. Importantly, macrophage activation was suppressed and M1/M2 macrophage polarization was regulated in colitis mice, and the percentage of CD11b+F4/80+ and CD11b+F4/80+TIM-1+ and CD11b+F4/80+iNOS+ decreased significantly and CD11b+F4/80+CD206+ and CD11b+F4/80+CD163+ increased significantly. Additionally, curcumin significantly downregulated CD11b+F4/80+TLR4+ macrophages and the protein levels of TLR2, TLR4, MyD88, NF-κBp65, p38MAPK, and AP-1 in colitis mice. Our study suggested that curcumin exerted therapeutic effects in colitis mice by regulating the balance of M1/M2 macrophage polarization and TLRs signaling pathway.


2021 ◽  
Author(s):  
Feng Zhu ◽  
Yihuan Chen ◽  
Jingjing Li ◽  
Ziying Yang ◽  
Yang Lin ◽  
...  

Abstract Background- Exosomes derived from human umbilical cord mesenchymal stem cells (UMSCs-Exo) were recommended as ideal substitutes for cell-free cardiac regenerative medicine, which had presented encouraging effects in regulating inflammation and attenuating myocardial injury. The phenotype of macrophages resident in myocardium were regulated dynamically in response to environmental cues, which may either protect against injury or promote maladaptive remodeling. However, the underlying mechanisms about UMSCs-Exo regulating macrophage polarization are still not well understood. Herein, we aimed to explore the effects of UMSCs-Exo on macrophage polarization and their roles in cardiac repair after myocardial infarction (MI). Methods and Results- Exosomes were isolated from the supernatant of human umbilical cord mesenchymal stem cells (UMSCs) and transplanted by intramyocardial injection after MI. Our results showed that UMSCs-Exo improved cardiac function by increasing M2 macrophage polarization and reducing excessive inflammation. After depletion of macrophages with clodronate liposomes, the therapeutic effects of UMSCs-Exo were disrupted. Administrated with UMSC-Exo, macrophages are inclined to polarize towards M2 phenotype in inflammatory environment in vitro. The results of RNA-sequencing indicated Plcb3 was a key gene concerned in UMSCs-Exo facilitated M2 macrophage polarization. Further bioinformatics analysis revealed exosomal miR-24-3p as a potential effector mediated Plcb3 down regulation in macrophages. Increasing miR-24-3p expression in macrophages effectively enhanced M2 macrophage polarization by suppressing Plcb3 expression and NF-κB pathway activation in inflammatory environment. Furthermore, diminishing miR-24-3p expression in UMSCs-Exo attenuated the effects of UMSCs-Exo on M2 macrophage polarization. Conclusions- Our study demonstrated that macrophages, as important inflammatory regulators, participated in UMSCs-Exo mediated myocardial repair after MI. And the therapeutical effects were at least partially carried out by UMSCs-Exo promoting M2 macrophage polarization in an inflammatory microenvironment. Mechanically, exosomal miR-24-3p inhibits the expression of Plcb3 and NF-κB pathway activation to promote M2 macrophage polarization.


Author(s):  
Roberta F.J. Criado ◽  
Paulo Ricardo Criado ◽  
Carla Pagliari ◽  
Mirian N. Sotto ◽  
Carlos D'Apparecida Machado Filho ◽  
...  

Author(s):  
Yuting Tang ◽  
Xiaofang Lin ◽  
Cheng Chen ◽  
Zhongyi Tong ◽  
Hui Sun ◽  
...  

Background: Nucleolin has multiple functions within cell survival and proliferation pathways. Our previous studies have revealed that nucleolin can significantly reduce myocardial ischemia-reperfusion injury by promoting myocardial angiogenesis and reducing myocardial apoptosis. In this study, we attempted to determine the role of nucleolin in myocardial infarction (MI) injury recovery and the underlying mechanism. Methods: Male BALB/c mice aged 6–8 weeks were used to set up MI models by ligating the left anterior descending coronary artery. Nucleolin expression in the heart was downregulated by intramyocardial injection of a lentiviral vector expressing nucleolin-specific small interfering RNA. Macrophage infiltration and polarization were measured by real-time polymerase chain reaction, flow cytometry, and immunofluorescence. Cytokines were detected by enzyme-linked immunosorbent assay. Results: Nucleolin expression in myocardium after MI induction decreased a lot at early phase and elevated at late phase. Nucleolin knockdown impaired heart systolic and diastolic functions and decreased the survival rate after MI. Macrophage infiltration increased in the myocardium after MI. Most macrophages belonged to the M1 phenotype at early phase (2 days) and the M2 phenotype increased greatly at late phase after MI. Nucleolin knockdown in the myocardium led to a decrease in M2 macrophage polarization with no effect on macrophage infiltration after MI. Furthermore, Notch3 and STAT6, key regulators of M2 macrophage polarization, were upregulated by nucleolin in RAW 264.7 macrophages. Conclusions: Lack of nucleolin impaired heart function during recovery after MI by reducing M2 macrophage polarization. This finding probably points to a new therapeutic option for ischemic heart disease.


2021 ◽  
Vol 22 (5) ◽  
pp. 2336
Author(s):  
Ryoka Uchiyama ◽  
Eriko Toyoda ◽  
Miki Maehara ◽  
Shiho Wasai ◽  
Haruka Omura ◽  
...  

Osteoarthritis of the knee (OAK) is a chronic degenerative disease and progresses with an imbalance of cytokines and macrophages in the joint. Studies regarding the use of platelet-rich plasma (PRP) as a point-of-care treatment for OAK have reported on its effect on tissue repair and suppression of inflammation but few have reported on its effect on macrophages and macrophage polarization. Based on our clinical experience with two types of PRP kits Cellaid Serum Collection Set P type kit (leukocyte-poor-PRP) and an Autologous Protein Solution kit (APS leukocyte-rich-PRP), we investigated the concentrations of humoral factors in PRPs prepared from the two kits and the effect of humoral factors on macrophage phenotypes. We found that the concentrations of cell components and humoral factors differed between PRPs purified using the two kits; APS had a higher concentration of M1 and M2 macrophage related factors. The addition of PRP supernatants to the culture media of monocyte-derived macrophages and M1 polarized macrophages revealed that PRPs suppressed M1 macrophage polarization and promoted M2 macrophage polarization. This research is the first to report the effect of PRPs purified using commercial kits on macrophage polarization.


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