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TEM1/endosialin/CD248 promotes pathologic scarring and TGF-β activity through its receptor stability in dermal fibroblasts

ABSTRACT: TEM1/endosialin/CD248 promotes pathologic scarring and TGF-β activity through its receptor stability in dermal fibroblasts

PROVIDER: PRJNA854626 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19909528_1.fastq.gz	Fastqsanger.gz
	SRR19909528_2.fastq.gz	Fastqsanger.gz
	SRR19909529_1.fastq.gz	Fastqsanger.gz
	SRR19909529_2.fastq.gz	Fastqsanger.gz
	SRR19909530_1.fastq.gz	Fastqsanger.gz

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TEM1/endosialin/CD248 promotes pathologic scarring and TGF-β activity through its receptor stability in dermal fibroblasts

Project description:We established a hypertrophic scar-like animal model using traction force in C57BL/6J mice to demonstrate the crucial mechanistic effect of TEM1 on pathological scarring. Samples from scar areas in sham and traction groups of Tem1WT/WT and Tem1lacZ/lacZ mice were subjected to RNA sequencing.

2024-02-09 | GSE207284 | GEO

TEM1/endosialin/CD248 promotes pathologic scarring and TGF-β activity through its receptor stability in dermal fibroblasts.

Project description:BackgroundPathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars.MethodsTo investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-β-mediated responses in pathologic scars.ResultsThe levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-β1 signaling through binding with and stabilizing TGF-β receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids.ConclusionsOur data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-β signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.

| S-EPMC10804696 | biostudies-literature

Lupus dermal fibroblasts hyper-respond to inflammatory cytokines and exhibit a pro-fibrotic phenotype to TGF-β in patients with scarring skin disease

Project description:we examined responses to cytokines in dermal fibroblasts from the skin of SLE patients with CLE and healthy control volunteers to identify the inflammatory phenotype and gene expression profile associated with SLE and scarring CLE lesions.

2024-04-03 | GSE237690 | GEO

JUN promotes hypertrophic skin scarring via CD36

Project description:Hypertrophic skin scarring following dermal injury causes extreme pain and psychological trauma for patients. Unfortuately, we do not have effective treatments to prevent or reverse skin scarring. Using RNA and ATAC sequencing of mouse and human fibroblasts, we show that JUN expressing fibroblasts are responsible for skin scarring by regulating CD36 expression. In summary, we show that CD36 antagonism by represent a therapeutic target to overcome JUN hypertrophic skin scarring.

2021-06-22 | GSE178562 | GEO

Dissecting CD248 role in tumor pericytes

Project description:We dissect CD248 gene function on tumor pericytes through RNA seq.

2019-10-23 | GSE139264 | GEO

Bulk RNA-seq of CD248+/- PDGFR-α+ cardiac fibroblasts

Project description:Post-injury remodeling is a complex process involving temporal specific cellular interactions in the injured tissue where the resident fibroblasts play multiple roles, including inflammation induction and tissue remodeling. To dissect the molecular basis of these interactions, we performed single-cell and spatial transcriptome analysis in human and mouse hearts after myocardial infarction. A subset of fibroblasts identified by unique high expression of CD248 was strongly correlated with collagen synthesis and remodeling, and genetic deletion of CD248 in fibroblast ameliorated cardiac fibrosis and dysfunction following ischemia/reperfusion, highlighting the functional importance of CD248 positive fibroblasts in post-injury pathological remodeling. CD248 stabilizes TGF-βR Ⅰ protein and activates ACKR3 expression in fibroblast, leading to enhanced T cell adhesion and retention. This CD248 mediated fibroblast-T cell interaction is required to sustain fibroblast activation and scar expansion in injured heart. Disruption of this interaction using monoclonal antibody or Chimeric antigen receptor T cell reduces T cell infiltration, ameliorates ischemia/reperfusion-induced cardiac fibrosis and improves heart function. Therefore, single cell and spatial molecular profiling in post-injury heart has uncovered a CD248 specific subclass of fibroblast with a critical role in fibroblast-T cell interaction and a new potential therapy to treat tissue fibrosis.

2025-01-24 | GSE287283 | GEO

Single-cell RNA Sequencing for CD248 cKO Mouse hearts at myocardial infarction model

Project description:Post-injury remodeling is a complex process involving temporal specific cellular interactions in the injured tissue where the resident fibroblasts play multiple roles, including inflammation induction and tissue remodeling. To dissect the molecular basis of these interactions, we performed single-cell and spatial transcriptome analysis in human and mouse hearts after myocardial infarction. A subset of fibroblasts identified by unique high expression of CD248 was strongly correlated with collagen synthesis and remodeling, and genetic deletion of CD248 in fibroblast ameliorated cardiac fibrosis and dysfunction following ischemia/reperfusion, highlighting the functional importance of CD248 positive fibroblasts in post-injury pathological remodeling. CD248 stabilizes TGF-βR Ⅰ protein and activates ACKR3 expression in fibroblast, leading to enhanced T cell adhesion and retention. This CD248 mediated fibroblast-T cell interaction is required to sustain fibroblast activation and scar expansion in injured heart. Disruption of this interaction using monoclonal antibody or Chimeric antigen receptor T cell reduces T cell infiltration, ameliorates ischemia/reperfusion-induced cardiac fibrosis and improves heart function. Therefore, single cell molecular profiling in post-injury heart has uncovered a CD248 specific subclass of fibroblast with a critical role in fibroblast-T cell interaction and a new potential therapy to treat tissue fibrosis.

2025-02-03 | GSE288103 | GEO

High-salt diet promotes hypertrophic scarring through TRPC3-mediated mitochondrial Ca2+ homeostasis dysfunction

Project description:Diet High in salt content have been associated with cardiovascular disease and chronic inflammation. We recently demonstrated that transient receptor potential canonical 3 (TRPC3) channels regulate myofibroblast transdifferentiation in hypertrophic scars. Here, we examined how high salt activation of TRPC3 participates in hypertrophic scarring during wound healing. In vitro, we confirmed that high salt increased the TRPC3 protein expression and the marker of myofibroblast alpha smooth muscle actin (α-SMA) in wild-type mice (WT) primary cultured dermal fibroblasts but not Trpc3-/- mice. Activation of TRPC3 by high salt elevated cytosolic Ca2+ influx and mitochondrial Ca2+ uptake in dermal fibroblasts in a TRPC3-dependent manner. High salt activation of TRPC3 enhanced mitochondrial respiratory dysfunction and excessive reactive oxygen species (ROS) production by inhibiting pyruvate dehydrogenase action, that activated ROS-triggered Ca2+ influx and the Rho kinase/MLC pathway in WT mice but not Trpc3-/- mice. In vivo, a persistent high-salt diet promoted myofibroblast transdifferentiation and collagen deposition in a TRPC3-dependent manner. Therefore, this study demonstrates that high salt enhances myofibroblast transdifferentiation and promotes hypertrophic scar formation through enhanced mitochondrial Ca2+ homeostasis, which activates the ROS-mediated pMLC/pMYPT1 pathway. TRPC3 deficiency antagonizes high salt diet-induced hypertrophic scarring. TRPC3 may be a novel target for hypertrophic scarring during wound healing.

2023-10-24 | PXD042087 | Pride

CD248 enhances mechanotransduction in specific fibroblasts subset responsible for scar formation to aggravate fibrosis in kidney

Project description:gene expression profiling of fibrotic kidney of unilateral ureteral obstruction (UUO) mice with or wothout CD248 knockout. The purose of this study was to confirm the gene expression changes of Cd248-/- fibrotic kidney compared with wild ype.

2025-08-24 | GSE241634 | GEO

Dissecting CD248 role in tumor pericytes

Project description:Dissecting CD248 role in tumor pericytes

| PRJNA578930 | ENA