Adiponectin Ameliorates GMH-Induced Brain Injury by Regulating Microglia M1/M2 Polarization Via AdipoR1/APPL1/AMPK/PPARγ Signaling Pathway in Neonatal Rats

Xu, Ningbo; Wei, Jun; Wei, Chunhua; He, Zhenyan; Doycheva, Desislava; Lenahan, Cameron; Tang, Wenhui; Zhou, Jian; Liu, Yanchao; Xu, Qian; Liu, Yahong; He, Xiaofu; Tang, Jiping; Zhang, Junyi

doi:10.3389/fimmu.2022.873382

Cited by 11 publications

(13 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it has been frequently reported that adiponectin regulates macrophage polarization by acting on AMPK, NF-kB, and PPAR-γ signaling [ 20 , 34 , 35 , 36 , 37 , 38 ]. However, according to our results, it has no effect on cellular morphology and migration.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, our study group analyzed the influence of adipokines, including leptin and adiponectin, on cementoblasts under compressive force stimulation, since adipose individuals showed worse outcome of orthodontic treatment [ 19 ]. In addition, adiponectin was reported to promote M2 polarization [ 20 ] and attenuate inflammation [ 21 ], and prevents tooth movement. Therefore, we assume it can intervene in the effects of compressive force on macrophages.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Wang

Groeger

Yong

et al. 2023

IJMS

View full text Add to dashboard Cite

Orthodontic tooth movement is a complex periodontal remodeling process triggered by compression that involves sterile inflammation and immune responses. Macrophages are mechanically sensitive immune cells, but their role in orthodontic tooth movement is unclear. Here, we hypothesize that orthodontic force can activate macrophages, and their activation may be associated with orthodontic root resorption. After force-loading and/or adiponectin application, the migration function of macrophages was tested via scratch assay, and Nos2, Il1b, Arg1, Il10, ApoE, and Saa3 expression levels were detected using qRT-PCR. Furthermore, H3 histone acetylation was measured using an acetylation detection kit. The specific inhibitor of H3 histone, I-BET762, was deployed to observe its effect on macrophages. In addition, cementoblasts were treated with macrophage-conditioned medium or compression force, and OPG production and cellular migration were measured. We further detected Piezo1 expression in cementoblasts via qRT-PCR and Western-blot, and its effect on the force-induced impairment of cementoblastic functions was also analyzed. Compressive force significantly inhibited macrophage migration. Nos2 was up-regulated 6 h after force-loading. Il1b, Arg1, Il10, Saa3, and ApoE increased after 24 h. Meanwhile, higher H3 histone acetylation was detected in the macrophages subjected to compression, and I-BET762 dampened the expression of M2 polarization markers (Arg1 and Il10). Lastly, even though the activated macrophage-conditioned medium showed no effect on cementoblasts, compressive force directly impaired cementoblastic function by enhancing mechanoreceptor Piezo1. Compressive force activates macrophages; specifically, it causes M2 polarization via H3 histone acetylation in the late stage. Compression-induced orthodontic root resorption is macrophage-independent, but it involves the activation of mechanoreceptor Piezo1.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Wang

Groeger

Yong

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The proteins were extracted from cells using the Keygen total protein extraction kit (Keygen, Biotech, Jiangsu, China) and then quantified by a bicinchoninic acid protein assay kit (Thermo Scientific, Waltham, MA, USA) as previously described [ 40 , 41 ]. The western blot experiments were performed according to standard procedures.…”

Section: Methodsmentioning

confidence: 99%

ALKBH5 promotes PD-L1-mediated immune escape through m6A modification of ZDHHC3 in glioma

Tang

Zhou

et al. 2022

Cell Death Discov.

Self Cite

View full text Add to dashboard Cite

N6-methylation of adenosine (m6A) is one of the most frequent chemical modifications in eukaryotic RNAs and plays a vital role in tumorigenesis and progression. Recently, emerging studies have shown that m6A modification by ALKBH5 was associated with immunotherapy response in various types of cancer. However, whether m6A demethylases ALKBH5 participate in regulating the tumor immune microenvironment and the efficacy of immunotherapy in glioblastoma remain unknown. Here, we found that deletion of ALKBH5 significantly inhibited the growth of glioma allografts, rescued the antitumoral immune response, and increased cytotoxic lymphocyte infiltration and proinflammatory cytokines in CSF while significantly suppressing PD-L1 protein expression. m6A-methylated RNA immunoprecipitation sequencing and RNA sequencing identify ZDDHC3 as the direct target of ALKBH5. Mechanically, ALKBH5 deficiency impairs the YTHDF2-mediated stability of ZDHHC3 mRNA, thereby suppressing PD-L1 expression by accelerating PD-L1 degradation in glioma. In addition, genetic deletion or pharmacological inhibition of ALKBH5 with IOX1 enhances the therapeutic efficacy of anti-PD-1 treatment in preclinical mice models. These data suggest that the combination of anti-PD-1 therapy and ALKBH5 inhibition may be a promising treatment strategy in glioma.

show abstract

“…Short-term neurofunctional behavior was evaluated using righting reflex and negative geotaxis tests, which were conducted on days 1 to 3 post-GMH by independent researchers blinded to information on experimental groups, as previously described. 7,15 Water Maze Test…”

Section: Short-term Neurobehavioral Assessmentmentioning

confidence: 99%

“…As previously described, Morris water maze trials were conducted to assess memory and spatial learning on days 21 to 28 post-GMH. 7,17 Nissl Staining…”

Section: Short-term Neurobehavioral Assessmentmentioning

confidence: 99%

Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPARγ Pathway After GMH

Chen

et al. 2023

Stroke

Self Cite

View full text Add to dashboard Cite

Background: Hematoma clearance has been a proposed therapeutic strategy for hemorrhagic stroke. This study investigated the impact of CX3CR1 (CX3C chemokine receptor 1) activation mediated by r-FKN (recombinant fractalkine) on hematoma resolution, neuroinflammation, and the underlying mechanisms involving AMPK (AMP-activated protein kinase)/PPARγ (peroxisome proliferator-activated receptor gamma) pathway after experimental germinal matrix hemorrhage (GMH). Methods: A total of 313 postnatal day 7 Sprague Dawley rat pups were used. GMH was induced using bacterial collagenase by a stereotactically guided infusion. r-FKN was administered intranasally at 1, 25, and 49 hours after GMH for short-term neurological evaluation. Long-term neurobehavioral tests (water maze, rotarod, and foot-fault test) were performed 24 to 28 days after GMH with the treatment of r-FKN once daily for 7 days. To elucidate the underlying mechanism, CX3CR1 CRISPR, or selective CX3CR1 inhibitor AZD8797, was administered intracerebroventricularly 24 hours preinduction of GMH. Selective inhibition of AMPK/PPARγ signaling in microglia via intracerebroventricularly delivery of liposome-encapsulated specific AMPK (Lipo-Dorsomorphin), PPARγ (Lipo-GW9662) inhibitor. Western blot, Immunofluorescence staining, Nissl staining, Hemoglobin assay, and ELISA assay were performed. Results: The brain expression of FKN and CX3CR1 were elevated after GMH. FKN was expressed on both neurons and microglia, whereas CX3CR1 was mainly expressed on microglia after GMH. Intranasal administration of r-FKN improved the short- and long-term neurobehavioral deficits and promoted M2 microglia polarization, thereby attenuating neuroinflammation and enhancing hematoma clearance, which was accompanied by an increased ratio of p-AMPK (phosphorylation of AMPK)/AMPK, Nrf2 (nuclear factor erythroid 2–related factor 2), PPARγ, CD36 (cluster of differentiation 36), CD163 (hemoglobin scavenger receptor), CD206 (the mannose receptor), and IL (interleukin)-10 expression, and decreased CD68 (cluster of differentiation 68), IL-1β, and TNF (tumor necrosis factor) α expression. The administration of CX3CR1 CRISPR or CX3CR1 inhibitor (AZD8797) abolished the protective effect of FKN. Furthermore, selective inhibition of microglial AMPK/PPARγ signaling abrogated the anti-inflammation effects of r-FKN after GMH. Conclusions: CX3CR1 activation by r-FKN promoted hematoma resolution, attenuated neuroinflammation, and neurological deficits partially through the AMPK/PPARγ signaling pathway, which promoted M1/M2 microglial polarization. Activating CX3CR1 by r-FKN may provide a promising therapeutic approach for treating patients with GMH.

show abstract

Adiponectin Ameliorates GMH-Induced Brain Injury by Regulating Microglia M1/M2 Polarization Via AdipoR1/APPL1/AMPK/PPARγ Signaling Pathway in Neonatal Rats

Cited by 11 publications

References 50 publications

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

ALKBH5 promotes PD-L1-mediated immune escape through m6A modification of ZDHHC3 in glioma

Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPARγ Pathway After GMH

Contact Info

Product

Resources

About