<scp>TGF</scp>β signalling pathway regulates angiogenesis by endothelial cells, in an adipose‐derived stromal cell/endothelial cell co‐culture 3D gel model

Lin, Shiyu; Xie, Jing; Gong, Tao; Shi, Sirong; Zhang, Tao; Fu, Na; Ye, Ling; Wang, Min; Lin, Yunfeng

doi:10.1111/cpr.12222

Cited by 15 publications

(8 citation statements)

References 32 publications

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“… 31 We first confirmed the increase of Lef-1 and cyclin D1 in ECs and ASCs after co-culture and detected the upregulation of VEGFα, a key growth factor acting through endothelial tyrosine kinase receptors, to promote the induction of the tip cell phenotype and the stimulation of both tip cell migration and stalk cell proliferation. 32 After screening the growth factors, we also found that bFGF and IGF-1 significantly increased in both ECs and ASCs, which suggested that these growth factors might be important paracrine factors in ASC-aided functional angiogenesis. 33 , 34 …”

Section: Discussionmentioning

confidence: 73%

Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling

et al. 2017

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Adipose-derived stromal cells (ASCs) have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial. In this study, we established a three-dimensional (3D) angiogenesis model by co-culturing ASCs and endothelial cells (ECs) in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel-based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC-mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear co-factor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A (VEGFA), basic fibroblast growth factor (bFGF), and insulin-like growth factor 1 (IGF-1). The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.

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Section: Discussionmentioning

confidence: 73%

Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling

et al. 2017

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“…Among its many functions, insulin-like growth factor 1 (IGF1) is recognized as an angiogenic factor, along with specific members of the VEGF, FGF, Bone Morphogenetic Protein (BMP), Tissue Growth Factor (TGF), and Hepatocyte Growth Factor (HGF) families. [14][15][16][17] However, the normal regulatory role of IGF1 in promoting angiogenesis is not particularly well understood as most research has focused upon its possible pathogenic participation in promoting aberrant vascularization during retinopathy and tumour growth. In addition, many reports are highly contradictory, perhaps reflecting the importance of the precise context of the studies and the pleiotropic nature of the growth factor and its receptor.…”

Section: Vascular Endothelial Growth Factor (Vegf) a And Fibroblast mentioning

confidence: 99%

Enhancing engineered vascular networks in vitro and in vivo: The effects of IGF1 on vascular development and durability

et al. 2017

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Objectives: Creation of functional, durable vasculature remains an important goal within the field of regenerative medicine. Engineered biological vasculature has the potential to restore or improve human tissue function. We hypothesized that the pleotropic effects of insulin-like growth factor 1 (IGF1) would enhance the engineering of capillary-like vasculature. Results: IGF1 supplementation significantly enhanced de novo vasculogenesis both in vitro and in vivo. Effects were long-term as they lasted the duration of the study period, and included network density, vessel length, and diameter. Bifurcation density was not affected. However, the highest concentrations of IGF1 tested were either ineffective or even deleterious. Sustained IGF1 delivery was required in vivo as the inclusion of recombinant IGF1 protein had minimal impact.Conclusion: IGF1 supplementation can be used to produce neovasculature with significantly enhanced network density and durability. Its use is a promising methodology for engineering de novo vasculature to support regeneration of functional tissue.

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“… 11 Angiogenesis is tightly regulated by a variety of factors, including pro-angiogenic and anti-angiogenic factors. 12 , 13 Pro-angiogenic factors include vascular endothelial growth factor (VEGF), 14 , 15 platelet-derived growth factor (PDGF), 15 , 16 and transforming growth factor β (TGF-β), 16 , 17 among others. VEGF is recognized as playing the vital role in the regulation of angiogenesis by stimulating the proliferation, migration, and tube formation of endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

linc00174-EZH2-ZNF24/Runx1-VEGFA Regulatory Mechanism Modulates Post-burn Wound Healing

Huang

Jiang

et al. 2020

Molecular Therapy - Nucleic Acids

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Preservation of denatured dermis exerts promotive functions in wound healing and improves the appearance and function of skin. Angiogenesis is crucial for wound healing during burn injury. However, the potential molecular mechanism of angiogenesis in the recovery after burn injury remains to be elucidated. Herein, RNA chromatin immunoprecipitation (ChIP) sequencing analysis revealed upregulation of long intergenic non-coding RNA 00174 (linc00174) in the post-burn tissues. linc00174 overexpression promoted angiogenic activities of human umbilical vein endothelial cells (HUVECs) in the heat-denatured cell model, characterized by the promotion of cell proliferation, migration, and tube formation. Mechanistically, linc00174 directly bound to enhancer of zeste homolog 2 (EZH2), thus stimulating the protein level of trimethylation at lysine 27 of histone H3 (H3K27me3). Moreover, inhibition of EZH2 resulted in downregulation of ZNF24 and Runx1, as well as a decline of vascular endothelial growth factor A (VEGFA). Furthermore, EZH2 modulated epigenetic repression of ZNF24 and Runx1 through the promoter of H3K27me3. Additionally, ZNF24 and Runx1 both functioned as transcriptional inhibitors of VEGFA. Taken together, these findings uncover that linc00174 epigenetically inhibits ZNF24 and Runx1 expression through binding to EZH2, thus attenuating the suppression of VEGFA, contributing to the facilitation of angiogenesis during the recovery of heat-denatured endothelial cells.

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TGFβ signalling pathway regulates angiogenesis by endothelial cells, in an adipose‐derived stromal cell/endothelial cell co‐culture 3D gel model

Cited by 15 publications

References 32 publications

Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling

Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling

Enhancing engineered vascular networks in vitro and in vivo: The effects of IGF1 on vascular development and durability

linc00174-EZH2-ZNF24/Runx1-VEGFA Regulatory Mechanism Modulates Post-burn Wound Healing

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