Aim: Prevascularization is vital to accelerate functional blood circulation establishment in transplanted engineered tissue constructs. Mesenchymal stem cells (MSCs) or mural cells could promote the survival of implanted endothelial cells (ECs) and enhance the stabilization of newly formed blood vessels. However, the dynamic cell-cell interactions between MSCs, mural cells and ECs in the angiogenic processes remain unclear. This study aimed to explore the interactions of human umbilical vein ECs (HUVECs) and dental pulp stem cells (DPSCs) in an in vitro cell coculture model.
Methodology: Human umbilical vascular ECs and DPSCs were directly cocultured or indirectly cocultured with transwell inserts in endothelial basal media-2 (EBM-2) supplemented with 5% FBS for 6 days. Expression of SMC-specific markers in DPSCs monoculture and HUVEC+DPSC cocultures was assessed by western blot and immunofluorescence. Activin A and transforming growth factor-beta 1 (TGF-β1) in conditioned media (CM) of HUVECs monoculture (E-CM), DPSCs monoculture (D-CM) and HUVEC+DPSC cocultures (E+D-CM) were analysed by enzyme-linked immunosorbent assay. TGF-β RI kinase inhibitor VI, SB431542, was used to block TGF-β1/ALK5 signalling in DPSCs.
Results: The expression of SMC-specific markers, α-SMA, SM22α and Calponin, were markedly increased in HUVEC+DPSC direct cocultures compared to that in DPSCs monoculture, while no differences were demonstrated between HUVEC+DPSC indirect cocultures and DPSCs monoculture. E+D-CM significantly upregulated the expression of SMC-specific markers in DPSCs compared to E-CM and D-CM. Activin A and TGF-β1 were considerably higher in E+D-CM than that in D-CM, with upregulated Smad2 phosphorylation in HUVEC+DPSC cocultures. Treatment with activin A did not change the expression of SMC-specific markers in DPSCs, while treatment with TGF-β1 significantly enhanced these markers' expression in DPSCs. In addition, blocking TGF-β1/ALK5 signalling inhibited the expression of α-SMA, SM22α and Calponin in DPSCs.
Conclusions: TGF-β1 was responsible for DPSC differentiation into SMCs in HUVEC+DPSC cocultures, and TGF-β1/ALK5 signalling pathway played a vital role in this process.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/iej.13943 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nox1/PAK1 is required for angiotensin II-induced vascular inflammation and abdominal aortic aneurysm formation.
Redox Biol
December 2024
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Guizhou Medical University, Gui'an, 561113, Guizhou, PR China. Electronic address:
NADPH oxidase 1 (Nox1) is a major isoform of Nox in vascular smooth muscle cells (VSMCs). VSMC activation and extracellular matrix (ECM) remodelling induce abdominal aortic aneurysm (AAA). In this study, we aim to determine the role of Nox1 in the progression of AAA and explore the underling mechanism.
View Article and Find Full Text PDFSmooth muscle cell-specific CD47 deletion suppresses atherosclerosis.
Life Sci
December 2024
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address:
Background: Recent smooth muscle cell (SMC)-lineage tracing and single-cell RNA sequencing (scRNA-seq) experiments revealed a significant role of SMC-derived cells in atherosclerosis development. Further, thrombospondin-1 (TSP1), a matricellular protein, and activation of its receptor cluster of differentiation (CD) 47 have been linked with atherosclerosis. However, the role of vascular SMC TSP1-CD47 signaling in regulating VSMC phenotype and atherogenesis remains unknown.
View Article and Find Full Text PDFDysfunction in either embryonic or postnatal vascular smooth muscle cells (SMCs) significantly contributes to the progression of various cardiovascular diseases. Therefore, elucidating the molecular mechanisms governing VSMC development and homeostasis is crucial. is the most reliable lineage gene for SMCs and has been utilized to develop tamoxifen-inducible Cre driver lines for achieving SMC-specific gene manipulation by crossing with mice carrying the lox -flanked gene, particularly in adult mice.
View Article and Find Full Text PDFIntroduction: Environmental exposure to dioxin has been linked to increased myocardial infarction. Smooth muscle cells (SMC) in the coronary vasculature play a critical role in atherosclerotic plaque remodeling due to their phenotypic plasticity, however, the detailed mechanism linking dioxin exposure to adverse SMC modulation is not well understood.
Methods: Single-cell RNA and ATAC sequencing and histological analyses were performed on the aorta from mouse models of atherosclerosis exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) or control.
Early growth response 1 exacerbates thoracic aortic aneurysm and dissection of mice by inducing the phenotypic switching of vascular smooth muscle cell through the activation of Krüppel-like factor 5.
Acta Physiol (Oxf)
November 2024
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Article Synopsis
- - The study investigates the role of Early Growth Response 1 (Egr1) in regulating vascular smooth muscle cells (VSMCs) and the progression of thoracic aortic aneurysm and dissection (TAAD).
- - Using mouse models, researchers found that Egr1 expression increased in TAAD conditions and its knockout reduced the severity of TAAD by preventing VSMC phenotypic switching.
- - The findings suggest that Egr1 promotes the harmful changes in VSMCs by enhancing the expression of Krüppel-like factor 5 (KLF5), indicating that targeting Egr1 could be a potential therapeutic strategy for TAAD.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!