Overexpression of integrin β2 improves migration and engraftment of adipose-derived stem cells and augments angiogenesis in myocardial infarction

Yuan, Zihui; Yan, Kai; Wang, Jian

doi:10.21037/atm-22-3339

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…In recent years, it has been found that ITGB2 mediates a metabolic switch in cancerassociated fibroblasts, promoting oral squamous cell carcinoma proliferation 18 . In a study on myocardial infarction, overexpression of ITGB2 increased the migration and improved the engraftment of adipose-derived stem cells and augmented angiogenesis 19 . Sequencing of carotid atherosclerosis samples showed that ITGB2 was a key gene 20 .…”

Section: Discussionmentioning

confidence: 99%

Identification of important genes related to HVSMC proliferation and migration in graft restenosis based on WGCNA

Liu,

Qin,

Chen

et al. 2024

Sci Rep

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The great saphenous vein is the most commonly used vessel for coronary artery bypass grafting (CABG), but its use has been associated with a high restenosis rate at 10-year follow-up. This study sought to determine the key genes associated with vein graft restenosis that could serve as novel therapeutic targets. A total of 3075 upregulated and 1404 downregulated genes were identified after transcriptome sequencing of three pairs of restenosed vein grafts and intraoperative spare great saphenous veins. Weighted gene co-expression network analysis showed that the floralwhite module had the highest correlation with vein graft restenosis. The intersection of the floralwhite module gene set and the upregulated gene set contained 615 upregulated genes strongly correlated with vein graft restenosis. Protein–protein interaction network analysis identified six hub genes (ITGAM, PTPRC, TLR4, TYROBP, ITGB2 and CD4), which were obtained using the STRING database and CytoHubba. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the common hub genes were mainly involved in the composition of the cell membrane; in biological processes such as neutrophil degranulation, receptor binding and intercellular adhesion, innate immune deficiency; and other signaling pathways. Finally, ITGB2 was selected as the target gene, and its expression was verified in tissues. The results showed that ITGB2 was significantly overexpressed in occluded vein grafts. To study the function of ITGB2 in HVSMCs, primary HVSMCs were cultured and successfully identified. EdU incorporation, wound healing and transwell assays showed that ITGB2 silencing significantly inhibited the proliferation and migration of HVSMCs stimulated by PDGF-BB. Overall, our study provides a basis for future studies on preventing restenosis following CABG.

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Section: Discussionmentioning

confidence: 99%

Identification of important genes related to HVSMC proliferation and migration in graft restenosis based on WGCNA

Liu,

Qin,

Chen

et al. 2024

Sci Rep

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“…Kdr in MCODE-5 drives meningeal vascular regeneration during head injury ( 37 ). In KEGG analysis of Itgb2 together with the proteins in PPI of MCODE, it was demonstrated that endothelial progenitor cell transplantation can promote neovascularization in ischemic tissues through ITGB2/IACM-1 interaction ( 31 , 38 ). And we speculated this might regulate the neovascularization process in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Single-cell analyses reveal the dynamic functions of Itgb2+ microglia subclusters at different stages of cerebral ischemia-reperfusion injury in transient middle cerebral occlusion mice model

et al. 2023

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IntroductionThe underlying pathophysiological mechanisms of cerebral ischemia reperfusion injury (CIRI) is intricate, and current studies suggest that neuron, astrocyte, microglia, endothelial cell, and pericyte all have different phenotypic changes of specific cell types after ischemic stroke. And microglia account for the largest proportion after CIRI. Previous transcriptomic studies of ischemic stroke have typically focused on the 24 hours after CIRI, obscuring the dynamics of cellular subclusters throughout the disease process. Therefore, traditional methods for identifying cell types and their subclusters may not be sufficient to fully unveil the complexity of single-cell transcriptional profile dynamics caused by an ischemic stroke.MethodsIn this study, to explore the dynamic transcriptional profile of single cells after CIRI, we used single-cell State Transition Across-samples of RNA-seq data (scSTAR), a new bioinformatics method, to analyze the single-cell transcriptional profile of day 1, 3, and 7 of transient middle cerebral artery occlusion (tMCAO) mice. Combining our bulk RNA sequences and proteomics data, we found the importance of the integrin beta 2 (Itgb2) gene in post-modeling. And microglia of Itgb2+ and Itgb2- were clustered by the scSTAR method. Finally, the functions of the subpopulations were defined by Matescape, and three different time points after tMCAO were found to exhibit specific functions.ResultsOur analysis revealed a dynamic transcriptional profile of single cells in microglia after tMCAO and explored the important role of Itgb2 contributed to microglia by combined transcriptomics and proteomics analysis after modeling. Our further analysis revealed that the Itgb2+ microglia subcluster was mainly involved in energy metabolism, cell cycle, angiogenesis, neuronal myelin formation, and repair at 1, 3, and 7 days after tMCAO, respectively.DiscussionOur results suggested that Itgb2+ microglia act as a time-specific multifunctional immunomodulatory subcluster during CIRI, and the underlying mechanisms remain to be further investigated.

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“…ASCs restored the expression of integrin β 2 that specifically blocks ICAM-1 and reduces macrophage accumulation in infarcted myocardium, increasing cell viability, proliferation, and migration [67]. In addition, ASC-derived exosomes mitigated MI-induced cardiac damage by promoting macrophage M2 polarization by restoring the expression of the sphingosine-1-phosphate receptor 1 (S1PR1) [68,69].…”

Section: Adipose-derived Stem Cells Preserve Heart Function In Precli...mentioning

confidence: 99%

Aging and Metabolic Reprogramming of Adipose-Derived Stem Cells Affect Molecular Mechanisms Related to Cardiovascular Diseases

Holvoet

2023

Cells

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We performed a systematic search of the PubMed database for English-language articles related to the function of adipose-derived stem cells in the pathogenesis of cardiovascular diseases. In preclinical models, adipose-derived stem cells protected arteries and the heart from oxidative stress and inflammation and preserved angiogenesis. However, clinical trials did not reiterate successful treatments with these cells in preclinical models. The low success in patients may be due to aging and metabolic reprogramming associated with the loss of proliferation capacity and increased senescence of stem cells, loss of mitochondrial function, increased oxidative stress and inflammation, and adipogenesis with increased lipid deposition associated with the low potential to induce endothelial cell function and angiogenesis, cardiomyocyte survival, and restore heart function. Then, we identify noncoding RNAs that may be mechanistically related to these dysfunctions of human adipose-derived stem cells. In particular, a decrease in let-7, miR-17-92, miR-21, miR-145, and miR-221 led to the loss of their function with obesity, type 2 diabetes, oxidative stress, and inflammation. An increase in miR-34a, miR-486-5p, and mir-24-3p contributed to the loss of function, with a noteworthy increase in miR-34a with age. In contrast, miR-146a and miR-210 may protect stem cells. However, a systematic analysis of other noncoding RNAs in human adipose-derived stem cells is warranted. Overall, this review gives insight into modes to improve the functionality of human adipose-derived stem cells.

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Overexpression of integrin β2 improves migration and engraftment of adipose-derived stem cells and augments angiogenesis in myocardial infarction

Cited by 8 publications

References 34 publications

Identification of important genes related to HVSMC proliferation and migration in graft restenosis based on WGCNA

Identification of important genes related to HVSMC proliferation and migration in graft restenosis based on WGCNA

Single-cell analyses reveal the dynamic functions of Itgb2+ microglia subclusters at different stages of cerebral ischemia-reperfusion injury in transient middle cerebral occlusion mice model

Aging and Metabolic Reprogramming of Adipose-Derived Stem Cells Affect Molecular Mechanisms Related to Cardiovascular Diseases

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