CD4 T-cells regulate angiogenesis and myogenesis

Kwee, Brian J.; Budina, Erica; Najibi, Alexander J.; Mooney, David J.

doi:10.1016/j.biomaterials.2018.06.003

Cited by 46 publications

(42 citation statements)

References 62 publications

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“…The pathogenesis of IPAH is complex and heterogeneous. Consistent with published data, the enrichment of these DEGs in GO terms, such as leukocyte migration [21,22], collagen-containing extracellular matrix (ECM) [23,24], cytokine activity [25,26] and antioxidant activity [27], con rms their involvement in the development of IPAH. Besides, enrichment of the identi ed DEGs in some KEGG pathways, such as the chemokine signaling pathway [25,26], IL-17 signaling pathway [28,29], and NF-kappa B signaling pathway [30,31] also suggests the relevance in IPAH pathogenesis.…”

Section: Discussionsupporting

confidence: 82%

Essential genes and miRNA-mRNA network contributing to the pathogenesis of idiopathic pulmonary arterial hypertension

Hao

Jiang

Xie

et al. 2020

Preprint

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Background: Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease. Owing to its high fatality rate and narrow therapeutic options, identification of the pathogenic mechanisms of IPAH is becoming increasingly important.Methods: In our research, we utilized the Robust Rank Aggregating (RRA) method to integrate four eligible PAH microarray datasets and identified the significant differentially expressed genes (DEGs) between IPAH and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to analyze their functions. The interaction network of protein-protein internet (PPI) was constructed to explore the correlation between these DEGs. The functional modules and hub genes were further identified by the weighted gene coexpression network analysis (WGCNA). Moreover, a miRNA microarray dataset was involved and analyzed to filter differentially expressed miRNA (DE-miRNAs). Potential target genes of screened DE-miRNAs were predicted and merged with DEGs to explore a miRNA-mRNA network in IPAH. Some hub genes were selected and validated by RT-PCR in lung tissues from PAH animal model.Results: A total of 260 DEGs, consisting of 183 upregulated and 77 down-regulated significant DEGs were identified, and some of those genes were novel. Their molecular roles in the etiology of IPAH remained vague. The most crucial functional module involved in IPAH mainly enriched in biological processes, including leukocyte migration, cell chemotaxis, and myeloid leukocyte migration. Construction and analysis of the PPI network showed that CXCL10, CXCL9, CCR1, CX3CR1, CX3CL1, CXCR2, CXCR1, PF4, CCL4L1, and ADORA3 were recognized as top10 hub genes with high connectivity degrees. WGCNA further identified five main functional modules involved in the pathogenesis of IPAH. 12 upregulated DE-miRNAs and 9 downregulated DE-miRNAs were identified. Among them, four downregulated DEGs, and eight upregulated DEGs were supposed to be negatively regulated by three upregulated DE-miRNAs, and three downregulated DE-miRNAs, respectively.Conclusions: This study identifies some key and functional coexpression modules involved in IPAH, as well as a potential IPAH-related miRNA-mRNA regulated network. It provides deepening insights into the molecular mechanisms and provides vital clues in seeking novel therapeutic targets for IPAH.

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Section: Discussionsupporting

confidence: 82%

Essential genes and miRNA-mRNA network contributing to the pathogenesis of idiopathic pulmonary arterial hypertension

Hao

Jiang

Xie

et al. 2020

Preprint

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“…CD4+ T cells play a major role in this transition. In a different muscle injury model of periphery artery disease, Kwee et al showed recently that conditioned media of Th2 and Th17 T-cells, delivered from an injectable alginate biomaterial into the ischemic hindlimb muscle of mice, enhanced angiogenesis and myogenesis 14 days post-delivery [42]. Therefore, we hypothesized that post-transplantation neovascularization will be enhanced in immunocompetent animals bearing all of the natural immune components compared to athymic nude immunocompromised mice, which lack T cells.…”

Section: Discussionmentioning

confidence: 95%

Enhanced Host Neovascularization of Prevascularized Engineered Muscle Following Transplantation into Immunocompetent versus Immunocompromised Mice

Perry

Merdler

Elishaev

et al. 2019

Cells

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Engineering of functional tissue, by combining either autologous or allogeneic cells with biomaterials, holds promise for the treatment of various diseases and injuries. Prevascularization of the engineered tissue was shown to enhance and improve graft integration and neovascularization post-implantation in immunocompromised mice. However, the neovascularization and integration processes of transplanted engineered tissues have not been widely studied in immunocompetent models. Here, we fabricated a three-dimensional (3D) vascularized murine muscle construct that was transplanted into immunocompetent and immunocompromised mice. Intravital imaging demonstrated enhanced neovascularization in immunocompetent mice compared to immunocompromised mice, 18 days post-implantation, indicating the advantageous effect of an intact immune system on neovascularization. Moreover, construct prevascularization enhanced neovascularization, integration, and myogenesis in both animal models. These findings demonstrate the superiority of implantation into immunocompetent over immunocompromised mice and, therefore, suggest that using autologous cells might be beneficial compared to allogeneic cells and subsequent immunosuppression. Taken together, these observations have the potential to advance the field of regenerative medicine and tissue engineering, ultimately reducing the need for donor organs and tissues.

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“…A number of studies have reported that different cytokines, such as IL-10, IL-12, IFN-γ, IL-17, IL-18 and IL-33, may play a role in the pathogenesis of CNV [33][34][35][36][37]. The pro-and anti-angiogenic effects of the cytokines relevant to Th1, Th2 and Th17 cells, participate in a complicated immunological network [38]. It has been reported that the number of macrophages increased significantly after laser photocoagulation [24], and M1-M2 polarization of macrophages have diverse distributions and functions in laser-induced CNV as well as in wet AMD [39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Altered Long Non-coding RNAs Involved in Immunological Regulation and Associated with Choroidal Neovascularization in Mice

et al. 2020

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Choroidal neovascularization (CNV) is a severe complication of the wet form of age-related macular degeneration (AMD). Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of different ocular neovascular diseases. To identify the function and therapeutic potential of lncRNAs in CNV, we assessed lncRNAs and mRNA expression profile in a mouse model of laser-induced CNV by microarray analysis. The results of altered lncRNAs were validated by qRT-PCR. Bioinformatics analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed to clarify the potential biological functions and signaling pathways with which altered genes are most closely related. Moreover, to identify the interaction of lncRNAs and mRNAs, we constructed a coding-non-coding gene co-expression (CNC) network. By microarray analysis, we identified 716 altered lncRNAs and 821 altered mRNAs in CNV mice compared to controls. A CNC network profile based on 7 validated altered lncRNAs (uc009ewo.1, AK148935, uc029sdr.1, ENSMUST00000132340, AK030988, uc007mds.1, ENSMUST00000180519) as well as 282 interacted and altered mRNAs, and were connected by 713 edges. GO and KEGG analyses suggested that altered mRNAs, as well as those lncRNA-interacted mRNAs were enriched in immune system process and chemokine signaling pathway. Thus, lncRNAs are significantly altered in this mouse model of CNV and are involved in immunological regulation, suggesting that lncRNAs may play a critical role in the pathogenesis of CNV. Thus, dysregulated lncRNAs and their target genes might be promising therapeutic targets to suppress CNV in AMD.

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CD4 T-cells regulate angiogenesis and myogenesis

Cited by 46 publications

References 62 publications

Essential genes and miRNA-mRNA network contributing to the pathogenesis of idiopathic pulmonary arterial hypertension

Essential genes and miRNA-mRNA network contributing to the pathogenesis of idiopathic pulmonary arterial hypertension

Enhanced Host Neovascularization of Prevascularized Engineered Muscle Following Transplantation into Immunocompetent versus Immunocompromised Mice

Altered Long Non-coding RNAs Involved in Immunological Regulation and Associated with Choroidal Neovascularization in Mice

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