CXCR4 blockade in macrophage promotes angiogenesis in ischemic hindlimb by modulating autophagy

Ma, Qunchao; Zhang, Ning; You, Yayu; Zhu, Junfeng; Yu, Zehui; Chen, Haibo; Xie, Xing; Yu, Hong

doi:10.1016/j.yjmcc.2022.05.002

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…CXCR4 is involved in various physiological processes such as haematopoiesis, immune response, neurogenesis, germ cell development, cardiogenesis, and angiogenesis 30 . CXCR4 expression inhibits macrophage autophagy and promotes macrophage polarisation towards the M1 type 31 . Our findings elucidated that CXCR4 was expressed in both CP and PD datasets.…”

Section: Discussionmentioning

confidence: 68%

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Elucidation of common molecular diagnostic biomarkers between chronic periodontitis and Parkinson's disease via bioinformatics analyses

Zehui,

Mengting,

Pengfei

et al. 2023

J of Periodontal Research

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Background and ObjectivesParkinson's disease (PD) and chronic periodontitis (CP) are both inflammatory diseases; a correlation between the two diseases has been reported, but the underlying mechanisms of this association have not been investigated. We investigated the common molecular mechanisms between PD and CP and the role of immune cells in the pathogenesis of them using bioinformatics analyses to elucidate the association between the two diseases.MethodsWe obtained gene expression data from the Gene Expression Omnibus (GEO) database: GSE10334, GSE16134, and GSE23586 for CP gingival samples and GSE20146 for PD brain samples. Subsequently, we conducted an enrichment analysis of the differentially expressed genes (DEGs) using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Moreover, all DEGs were analysed for protein–transcription factor interactions and protein–immune cell co‐expression. We constructed protein–transcription factor, protein–protein interaction (PPI), and protein–immune cell co‐expression networks using the Cytoscape software. Moreover, we identified the hub genes and investigated them for potential diagnostic value.Results and ConclusionWe identified 99 DEGs in the three CP datasets, 520 DEGs in the PD dataset and found five common DEGs in the CP and PD datasets, namely CXCR4, CXCL8, CD19, RPTN, and SLC16A9. These common DEGs identified in our study may have a potential impact on disease pathogenesis through the involvement of CXCR4‐CXCL8‐CD19 protein‐complexes in dendritic cells. Therefore, CD19, LCP2, CXCR4, and LYN could be used as target molecules for the clinical diagnosis of both diseases.

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Section: Discussionmentioning

confidence: 68%

“…30 CXCR4 expression inhibits macrophage autophagy and promotes macrophage polarisation towards the M1 type. 31 Our findings elucidated that CXCR4 was expressed in both CP and PD datasets. This may be because CXCR4 regulates the inflammatory state of these two diseases and is involved in disease onset and progression.…”

Section: Discussionmentioning

confidence: 69%

Elucidation of common molecular diagnostic biomarkers between chronic periodontitis and Parkinson's disease via bioinformatics analyses

Zehui,

Mengting,

Pengfei

et al. 2023

J of Periodontal Research

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“…Moreover, in order to test whether CXCR4BP-lipid improves targeting and cellular uptake of HV, we examined the cellular uptake of HV modified with or without CXCR4BP-lipid. After 3 h of incubation, we observed a significantly higher cellular uptake of HV(Mn 2+ /Dox) with CXCR4BP-lipid among J774A.1 cells, compared to HV(Mn 2+ /Dox) without CXCR4BP-lipid (Figure C), suggesting the efficient intracellular delivery of CXCR4-targeted HV(Mn 2+ /Dox) into macrophage cells known to express high levels of CXCR4. , …”

Section: Resultsmentioning

confidence: 84%

“…After 3 h of incubation, we observed a significantly higher cellular uptake of HV(Mn 2+ / Dox) with CXCR4BP-lipid among J774A.1 cells, compared to HV(Mn 2+ /Dox) without CXCR4BP-lipid (Figure 5C), suggesting the efficient intracellular delivery of CXCR4targeted HV(Mn 2+ /Dox) into macrophage cells known to express high levels of CXCR4. 38,39 Next, we investigated whether HV(Mn 2+ /Dox) can polarize nai ̈ve J774A.1 cells (representing M0-like macrophages) toward the M1 phenotype. The immunomodulatory effect of HV(Mn 2+ /Dox) on macrophages was assessed by measuring the expression of surface markers associated with M1 polarization using flow cytometry.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

CXCR4-Targeted Macrophage-Derived Biomimetic Hybrid Vesicle Nanoplatform for Enhanced Cancer Therapy through Codelivery of Manganese and Doxorubicin

Jang,

Cho,

Kim

et al. 2024

ACS Appl. Mater. Interfaces

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Immune-cell-derived membranes have garnered significant attention as innovative delivery modalities in cancer immunotherapy for their intrinsic immune-modulating functionalities and superior biocompatibilities. Integrating additional parental cell membranes or synthetic lipid vesicles into cellular vesicles can further potentiate their capacities to perform combinatorial pharmacological activities in activating antitumor immunity, thus providing insights into the potential of hybrid cellular vesicles as versatile delivery vehicles for cancer immunotherapy. Here, we have developed a macrophage-membrane-derived hybrid vesicle that has the dual functions of transporting immunotherapeutic drugs and shaping the polarization of tumor-associated macrophages for cancer immunotherapy. The platform combines M1 macrophage-membrane-derived vesicles with CXCR4-binding-peptide-conjugated liposomes loaded with manganese and doxorubicin. The hybrid nanovesicles exhibited remarkable macrophage-targeting capacity through the CXCR4-binding peptide, resulting in enhanced macrophage polarization to the antitumoral M1 phenotype characterized by proinflammatory cytokine release. The manganese/doxorubicin-loaded hybrid vesicles in the CXCR4-expressing tumor cells evoked potent cancer cytotoxicity, immunogenic cell death of tumor cells, and STING activation. Moreover, cotreatment with manganese and doxorubicin promoted dendritic cell maturation, enabling effective tumor growth inhibition. In murine models of CT26 colon carcinoma and 4T1 breast cancer, intravenous administration of the manganese/doxorubicin-loaded hybrid vesicles elicited robust tumor-suppressing activity at a low dosage without adverse systemic effects. Local administration of hybrid nanovesicles also induced an abscessive effect in a bilateral 4T1 tumor model. This study demonstrates a promising biomimetic manganese/doxorubicin-based hybrid nanovesicle platform for effective cancer immunotherapy tailored to the tumor microenvironment, which may offer an innovative approach to combinatorial immunotherapy.

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“…Furthermore, the CXCR4 receptor exerts a critical effect on SDF-1α-induced autophagy in chondrocytes by inhibiting mTOR signaling, a key autophagy regulatory pathway. Interestingly, CXCR4 deficiency in macrophages is associated with enhanced autophagy and reduced expression of decorin and inflammatory cytokines ( 41 ). This result suggested that CXCR4 may modulate autophagy in macrophages, thereby affecting inflammation and angiogenesis under ischemic conditions.…”

Section: Discussionmentioning

confidence: 99%

Investigation of autophagy‑related genes and immune infiltration in calcific aortic valve disease: A bioinformatics analysis and experimental validation

Hu,

Jiang,

Yang

et al. 2024

Exp Ther Med

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The present study aimed to elucidate the role of autophagy-related genes (ARGs) in calcific aortic valve disease (CAVD) and their potential interactions with immune infiltration via experimental verification and bioinformatics analysis. A total of three microarray datasets (GSE12644, GSE51472 and GSE77287) were obtained from the Gene Expression Omnibus database, and gene set enrichment analysis was performed to identify the relationship between autophagy and CAVD. After differentially expressed genes and differentially expressed ARGs (DEARGs) were identified using CAVD samples and normal aortic valve samples, a functional analysis was performed, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, protein-protein interaction network construction, hub gene identification and validation, immune infiltration and drug prediction. The results of the present study indicated a significant relationship between autophagy and CAVD. A total of 46 DEARGs were identified. GO and pathway enrichment analyses revealed the complex roles of DEARGs in regulating CAVD, including multiple gene functions and pathways. A total of 10 hub genes were identified, with three (SPP1, CXCL12 and CXCR4) consistently upregulated in CAVD samples compared with normal aortic valve samples in multiple datasets and experimental validation. Immune infiltration analyses demonstrated significant differences in immune cell proportions between CAVD samples and normal aortic valve samples, thus showing the crucial role of immune infiltration in CAVD development. Furthermore, therapeutic drugs were predicted that could target the identified hub genes, including bisphenol A, resveratrol, progesterone and estradiol. In summary, the present study illuminated the crucial role of autophagy in CAVD development and identified key ARGs as potential therapeutic targets. In addition, the observed immune cell infiltration and predicted autophagy-related drugs suggest promising avenues for future research and novel CAVD treatments.

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CXCR4 blockade in macrophage promotes angiogenesis in ischemic hindlimb by modulating autophagy

Cited by 6 publications

References 49 publications

Elucidation of common molecular diagnostic biomarkers between chronic periodontitis and Parkinson's disease via bioinformatics analyses

Elucidation of common molecular diagnostic biomarkers between chronic periodontitis and Parkinson's disease via bioinformatics analyses

CXCR4-Targeted Macrophage-Derived Biomimetic Hybrid Vesicle Nanoplatform for Enhanced Cancer Therapy through Codelivery of Manganese and Doxorubicin

Investigation of autophagy‑related genes and immune infiltration in calcific aortic valve disease: A bioinformatics analysis and experimental validation

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