Activating α7nAChR helps post-myocardial infarction healing by regulating macrophage polarization via the STAT3 signaling pathway

Niu, Xiao‐Hui; Liu, Ronghua; Xiao, Lihua; He, Rui‐Lin; Lv, Fang-Zhou; Wu, Shu-jie; Xu-qing, LI; Li, Lei; Lin, Jiafeng

doi:10.1007/s00011-023-01714-2

Cited by 5 publications

(2 citation statements)

References 64 publications

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“…In murine bone marrow-derived macrophages, it has been shown that the stimulation of α7nAChR activates the STAT3 prosurvival pathway, which serves as a protective mechanism against endoplasmic reticulum stress-induced apoptosis [73]. Additionally, studies conducted on rats with myocardial infarction have demonstrated that the administration of a specific α7-nAChR agonist (PNU 282,987) reduces the infiltration of inflammatory M1 macrophages into the infarcted area and increases the recruitment of M2-type anti-inflammatory peripheral macrophages to the infarcted tissue [74]. Moreover, in vitro studies using rodent cells focused on atherosclerosis have shown that CAR agonists (ACh and GTS-21) suppress M1 macrophage polarization while promoting M2 macrophage polarization through the upregulation of TNFAIP3 and phosphorylation of STAT3 [75].…”

Section: The Cholinergic Anti-inflammatory Response (Car) Is Closely ...mentioning

confidence: 99%

Cholinergic Polarization of Human Macrophages

Roa-Vidal,

Rodríguez-Aponte,

Lasalde-Dominicci

et al. 2023

IJMS

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Macrophages serve as vital defenders, protecting the body by exhibiting remarkable cellular adaptability in response to invading pathogens and various stimuli. These cells express nicotinic acetylcholine receptors, with the α7-nAChR being extensively studied due to its involvement in activating the cholinergic anti-inflammatory pathway. Activation of this pathway plays a crucial role in suppressing macrophages’ production of proinflammatory cytokines, thus mitigating excessive inflammation and maintaining host homeostasis. Macrophage polarization, which occurs in response to specific pathogens or insults, is a process that has received limited attention concerning the activation of the cholinergic anti-inflammatory pathway and the contributions of the α7-nAChR in this context. This review aims to present evidence highlighting how the cholinergic constituents in macrophages, led by the α7-nAChR, facilitate the polarization of macrophages towards anti-inflammatory phenotypes. Additionally, we explore the influence of viral infections on macrophage inflammatory phenotypes, taking into account cholinergic mechanisms. We also review the current understanding of macrophage polarization in response to these infections. Finally, we provide insights into the relatively unexplored partial duplication of the α7-nAChR, known as dup α7, which is emerging as a significant factor in macrophage polarization and inflammation scenarios.

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Section: The Cholinergic Anti-inflammatory Response (Car) Is Closely ...mentioning

confidence: 99%

Cholinergic Polarization of Human Macrophages

Roa-Vidal,

Rodríguez-Aponte,

Lasalde-Dominicci

et al. 2023

IJMS

View full text Add to dashboard Cite

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“…After the infarct area is cleared of cell debris, pro-inflammatory macrophages begin to undergo apoptosis, and newly arrived and differentiated macrophages polarize to anti-inflammatory M2 phenotype which facilitates the resolution of inflammation and tissue repair, peaking on day 7 post-AMI. [4][5][6] These unique characteristics of macrophages can be a promising target in facilitating cardiac repair for AMI.…”

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confidence: 99%

Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway

Gong,

Xiong,

Ning

et al. 2024

IJN

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Background Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSC NIC -exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). Methods MSC NIC -exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSC NIC -exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Results Compared to MSC-exo, MSC NIC -exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68 + CD206 + / CD68 + cells in infarcted hearts 3 days post-infarction. The notable ability of MSC NIC -exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSC NIC -exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. Conclusion This study suggested that MSC NIC -exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.

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Retinal Microenvironment‐Protected Rhein‐GFFYE Nanofibers Attenuate Retinal Ischemia‐Reperfusion Injury via Inhibiting Oxidative Stress and Regulating Microglial/Macrophage M1/M2 Polarization

Zhang,

Peng,

et al. 2023

Advanced Science

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Retinal ischemia is involved in the occurrence and development of various eye diseases, including glaucoma, diabetic retinopathy, and central retinal artery occlusion. To the best of our knowledge, few studies have reported self‐assembling peptide natural products for the suppression of ocular inflammation and oxidative stress. Herein, a self‐assembling peptide GFFYE is designed and synthesized, which can transform the non‐hydrophilicity of rhein into an amphiphilic sustained‐release therapeutic agent, and rhein‐based therapeutic nanofibers (abbreviated as Rh‐GFFYE) are constructed for the treatment of retinal ischemia‐reperfusion (RIR) injury. Rh‐GFFYE significantly ameliorates oxidative stress and inflammation in an in vitro oxygen‐glucose deprivation (OGD) model of retinal ischemia and a rat model of RIR injury. Rh‐GFFYE also significantly enhances retinal electrophysiological recovery and exhibits good biocompatibility. Importantly, Rh‐GFFYE also promotes the transition of M1‐type macrophages to the M2 type, ultimately altering the pro‐inflammatory microenvironment. Further investigation of the treatment mechanism indicates that Rh‐GFFYE activates the PI3K/AKT/mTOR signaling pathway to reduce oxidative stress and inhibits the NF‐κB and STAT3 signaling pathways to affect inflammation and macrophage polarization. In conclusion, the rhein‐loaded nanoplatform alleviates RIR injury by modulating the retinal microenvironment. The findings are expected to promote the clinical application of hydrophobic natural products in RIR injury‐associated eye diseases.

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Activating α7nAChR helps post-myocardial infarction healing by regulating macrophage polarization via the STAT3 signaling pathway

Cited by 5 publications

References 64 publications

Cholinergic Polarization of Human Macrophages

Cholinergic Polarization of Human Macrophages

Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway

Retinal Microenvironment‐Protected Rhein‐GFFYE Nanofibers Attenuate Retinal Ischemia‐Reperfusion Injury via Inhibiting Oxidative Stress and Regulating Microglial/Macrophage M1/M2 Polarization

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