HtrA3‐Mediated Endothelial Cell–Extracellular Matrix Crosstalk Regulates Tip Cell Specification

Guo, Yaru; Ma, Siqin; Xu, Mingming; Wei, Yan; Zhang, Xuehui; Huang, Ying; He, Yayi; Heng, Boon Chin; Chen, Lili; Deng, Xuliang

doi:10.1002/adfm.202100633

Cited by 6 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In general, angiogenesis is initiated from a pre-existing vasculature by sprouting ECs . The physiological process of angiogenesis includes a number of stages.…”

Section: Resultsmentioning

confidence: 99%

Drug-Delivery Nanoplatform with Synergistic Regulation of Angiogenesis–Osteogenesis Coupling for Promoting Vascularized Bone Regeneration

Zhu

Zhang

et al. 2023

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

It has been confirmed that substantial vascularization is an effective strategy to heal large-scale bone defects in the field of bone tissue engineering. The local application of deferoxamine (DFO) is among the most common and effective methods for promoting the formation of blood vessels, although its short half-life in plasma, rapid clearance, and poor biocompatibility limit its therapeutic suitability. Herein, zeolitic imidazolate framework-8 (ZIF-8) was selected as a vehicle to extend the halflife of DFO. In the present study, a nano DFO-loaded ZIF-8 (DFO@ZIF-8) drug delivery system was established to promote angiogenesis−osteogenesis coupling. The nanoparticles were characterized, and their drug loading efficiency was examined to confirm the successful synthesis of nano DFO

show abstract

“…In general, angiogenesis is initiated from a pre-existing vasculature by sprouting ECs . The physiological process of angiogenesis includes a number of stages.…”

Section: Resultsmentioning

confidence: 99%

Drug-Delivery Nanoplatform with Synergistic Regulation of Angiogenesis–Osteogenesis Coupling for Promoting Vascularized Bone Regeneration

Zhu

Zhang

et al. 2023

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…Moreover, a network-Based analysis showed that PI3K/Akt signaling pathway and Rap1 signaling pathway in human vascular endothelial cells were the two pathways that differentiate into tip cells and stalk cells [ 35 ]. A report displayed that HtrA3 in HUVECs can enhance sprouting, cellular cortical protrusions, and mobility of HUVECs and further promote tip cell formation and tip position competition by activating PI3K/Akt signaling pathway [ 36 ]. In our study, we also found that CRC-CDEs and exosomal circTUBGCP4 can activate Akt signaling pathway to promote tip cell formation in vascular endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Exosomal circTUBGCP4 promotes vascular endothelial cell tipping and colorectal cancer metastasis by activating Akt signaling pathway

Chen

Liu

et al. 2023

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Exosome is crucial mediator and play an important role in tumor angiogenesis. Tip cell formation is a prerequisite for persistent tumor angiogenesis which causes tumor metastasis. However, the functions and underlying mechanisms of tumor cell-derived exosomes in angiogenesis and tip cell formation remain less understood. Methods Exosomes derived from serum of colorectal cancer (CRC) patients with metastasis/non-metastasis and CRC cells were isolated by ultracentrifugation. CircRNAs in these exosomes were analyzed by circRNA microarray. Then, exosomal circTUBGCP4 was identified and verified by quantitative real-time PCR (qRT–PCR) and in situ hybridization (ISH). Loss- and gain-of-function assays were performed to explore the effect of exosomal circTUBGCP4 on vascular endothelial cell tipping and colorectal cancer metastasis in vitro and in vivo. Mechanically, bioinformatics analysis, biotin-labeled circTUBGCP4/ miR-146b-3p RNA pulldown, RNA immunoprecipitation (RIP), and luciferase reporter assay were used to confirm the interaction among circTUBGCP4, miR-146b-3p, and PDK2. Results Here, we showed that exosomes derived from CRC cells enhanced vascular endothelial cell migration and tube formation via inducing filopodia formation and endothelial cell tipping. We further screened the upregulated circTUBGCP4 in serum of CRC patients with metastasis compared to non-metastasis. Silencing circTUBGCP4 expression in CRC cell-derived exosomes (CRC-CDEs) inhibited endothelial cell migration, tube formation, tip cell formation, and CRC metastasis. Overexpression of circTUBGCP4 had opposite results in vitro and in vivo. Mechanically, circTUBGCP4 upregulated PDK2 to activate Akt signaling pathway by sponging miR-146b-3p. Moreover, we found that miR-146b-3p could be a key regulator for vascular endothelial cell dysfunction. Exosomal circTUBGCP4 promoted tip cell formation and activated the Akt signaling pathway by inhibiting miR-146b-3p. Conclusions Our results suggest that colorectal cancer cells generate exosomal circTUBGCP4, which causes vascular endothelial cell tipping to promote angiogenesis and tumor metastasis by activating Akt signaling pathway.

show abstract

“…Tissue processing and sectioning were carried out as previously described 38 . Images were captured using confocal microscopy (Leica).…”

Section: Methodsmentioning

confidence: 99%

Matrix stiffness regulates macrophage polarisation via the Piezo1‐YAP signalling axis

Mei,

Guo,

Wang

et al. 2024

Cell Proliferation

Self Cite

View full text Add to dashboard Cite

Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro‐ and anti‐inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well‐established, but how physical cues regulate macrophage function that may play a fundamental role in implant‐bone interface, remains poorly understood. Here we find that bone marrow‐derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states. BMDM are ‘primed’ to a pro‐inflammatory M1 phenotype on stiff substrates, while to an anti‐inflammatory M2 phenotype on soft and medium stiffness substrates. It is further observed that matrix stiffening increases Piezo1 expression, as well as leads to subsequent activation of the mechanotransduction signalling effector YAP, thus favouring M1 polarisation whilst suppressing M2 polarisation. Moreover, upon treatment with YAP inhibitor, we successfully induce macrophage re‐polarisation to the M2 state within the implant site microenvironment, which in turn promotes implant osseointegration. Collectively, our present study thus characterises the critical role of the Piezo1‐YAP signalling axis in macrophage mechanosensing and stiffness‐mediated macrophage polarisation and provides cues for the design of immuno‐modulatory biomaterials that can regulate the macrophage phenotype.

show abstract

HtrA3‐Mediated Endothelial Cell–Extracellular Matrix Crosstalk Regulates Tip Cell Specification

Cited by 6 publications

References 46 publications

Drug-Delivery Nanoplatform with Synergistic Regulation of Angiogenesis–Osteogenesis Coupling for Promoting Vascularized Bone Regeneration

Drug-Delivery Nanoplatform with Synergistic Regulation of Angiogenesis–Osteogenesis Coupling for Promoting Vascularized Bone Regeneration

Exosomal circTUBGCP4 promotes vascular endothelial cell tipping and colorectal cancer metastasis by activating Akt signaling pathway

Matrix stiffness regulates macrophage polarisation via the Piezo1‐YAP signalling axis

Contact Info

Product

Resources

About