Keloid fibroproliferative properties are dependent on stem cells modified by the HEDGEHOG-GLI1 pathway [EA1488]
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ABSTRACT:
PROVIDER: PRJNA906140 | ENA |
REPOSITORIES: ENA
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Project description:Keloids are benign fibroproliferative skin tumors caused by aberrant wound healing, the etiology of which is unknown. Although keloids cause life inconveniences and cosmetic problems, the lack of animal models has yet to elucidate their pathogenesis or develop effective treatments. Here, we found that the characteristics of stem cells from keloid lesions and surrounding dermis differ from those of normal skin and that HEDGEHOG (HH) signal and its downstream transcription factor GLI1 were upregulated in keloid patient-derived stem cells. Inhibition of the HH-GLI1 pathway reduced the expression of genes involved in keloids and fibrosis-inducing cytokines, including osteopontin. Moreover, HH-signal inhibitor vismodegib reduced keloid reconstituted tumor size and the expression of keloid related genes in nude mouse, and the collagen bundle and the expression of cytokines characteristic for keloids in ex vivo culture of keloid tissues. These results implicate the HH-GLI1 pathway in keloid pathogenesis and suggest therapeutic target of keloids.
2023-12-13 | GSE218894 | GEO
Project description:Keloids are benign fibroproliferative skin tumors caused by aberrant wound healing, the etiology of which is unknown. Although keloids cause life inconveniences and cosmetic problems, the lack of animal models has yet to elucidate their pathogenesis or develop effective treatments. Here, we found that the characteristics of stem cells from keloid lesions and surrounding dermis differ from those of normal skin and that HEDGEHOG (HH) signal and its downstream transcription factor GLI1 were upregulated in keloid patient-derived stem cells. Inhibition of the HH-GLI1 pathway reduced the expression of genes involved in keloids and fibrosis-inducing cytokines, including osteopontin. Moreover, HH-signal inhibitor vismodegib reduced keloid reconstituted tumor size and the expression of keloid related genes in nude mouse, and the collagen bundle and the expression of cytokines characteristic for keloids in ex vivo culture of keloid tissues. These results implicate the HH-GLI1 pathway in keloid pathogenesis and suggest therapeutic target of keloids.
2023-12-13 | GSE218922 | GEO
Project description:Keloid fibroproliferative properties are dependent on stem cells modified by the HEDGEHOG-GLI1 pathway
| PRJNA906131 | ENA
Project description:Keloid fibroproliferative properties are dependent on stem cells modified by the HEDGEHOG-GLI1 pathway [EA1874]
| PRJNA906088 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-12-13 | GSE218923 | GEO
Project description:Keloid disease (KD) is a fibroproliferative cutaneous tumour characterised by heterogeneity, excess collagen deposition and aggressive local invasion. Normal and keloid scar tissues were analysed with a site-specific in situ approach through combined laser capture microdissection, as well as whole tissue biopsy and monolayer cell culture techniques.
2017-12-07 | E-MTAB-4945 | biostudies-arrayexpress
Project description:Keloid is a dermal fibroproliferative disease with various etiologies and unclear pathogenesis. Recent studies have revealed that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) exerted regulatory functions through a competing endogenous RNA (ceRNA) pathway in keloid progression. However, the expression profiles of circRNAs and lncRNAs in keloid dermal tissues (KDTs) remain unknown. This study aimed to identify differentially expressed circRNAs, lncRNAs and genes in KDTs.
2023-09-07 | GSE212954 | GEO
Project description:Keloids are wounding-induced fibroproliferative human tumor–like skin scars of complex genetic makeup and poorly defined pathogenesis. Fibroblasts are the principal mediator of fibroproliferative disorders. To reveal dynamic epigenetic and transcriptome changes of keloid fibroblasts, a vertical study from RNA-seq and ATAC-seq analyses followed by in vivo confirmation of candidate molecule expression and subsequent functional testing was carried out using an early passage, freshly isolated keloid fibroblast cell strain and its paired normal control. These keloid fibroblasts produce keloid-like scars in a plasma clot-based skin equivalent humanized keloid animal model. RNA-seq analysis reveals that Hepatic fibrosis is the most significant pathway followed by Wnt–b-catenin signaling, TGF-b signaling, regulation of the EMT pathway, the STAT3 pathway, and adherens junction signaling. ATAC-seq analysis shows that STAT3 signaling is the most active pathway in keloid fibroblasts, followed by Wnt signaling (Wnt5) and regulation of the EMT pathway. Immunohistochemistry confirms that activated STAT3, (Tyr705 phospho-STAT3) and/or b-catenin are upregulated in dermal fibroblasts of keloid clinical specimens and mature keloid skin equivalent implants from the humanized mouse model compared to the normal control. The effect of STAT3 signaling on keloid fibroblast collagen expression was further tested in plasma clot-based skin equivalents using Cucurbitacin I, a selective JAK2/STAT3 inhibitor. A non-linear dose response of Cucurbitacin I was observed in collagen type I expression indicating a likely role of STAT3 signaling pathway in keloid pathogenesis. This work also demonstrates the utility of the recently established humanized keloid mouse model in exploring the mechanism of keloid formation.
2020-01-11 | GSE125022 | GEO
Project description:Keloids are benign fibroproliferative skin tumors caused by aberrant wound healing that can negatively impact patient quality of life. The lack of animal models has limited research on pathogenesis or developing effective treatments, and the etiology of keloids remains unknown. Here, we found that the characteristics of stem-like cells from keloid lesions and the surrounding dermis differ from those of normal skin. Furthermore, the HEDGEHOG (HH) signal and its downstream transcription factor GLI1 were upregulated in keloid patient-derived stem-like cells. Inhibition of the HH-GLI1 pathway reduced the expression of genes involved in keloids and fibrosis-inducing cytokines, including osteopontin. Moreover, the HH signal inhibitor vismodegib reduced keloid reconstituted tumor size and keloid-related gene expression in nude mice and the collagen bundle and expression of cytokines characteristic for keloids in ex vivo culture of keloid tissues. These results implicate the HH-GLI1 pathway in keloid pathogenesis and suggest therapeutic targets of keloids.
| S-EPMC10703807 | biostudies-literature
Project description:The morphogen and mitogen, Sonic Hedgehog, activates a Gli1-dependent transcription program that drives proliferation of granule neuron progenitors (GNPs) within the external germinal layer of the postnatally developing cerebellum. Medulloblastomas with mutations activating the Sonic Hedgehog signaling pathway preferentially arise within the external germinal layer, and the tumor cells closely resemble GNPs. Atoh1/Math1, a basic helix-loop-helix transcription factor essential for GNP histogenesis, does not induce medulloblastomas when expressed in primary mouse GNPs that are explanted from the early postnatal cerebellum and transplanted back into the brains of naïve mice. However, enforced expression of Atoh1 in primary GNPs enhances the oncogenicity of cells overexpressing Gli1 by almost three orders of magnitude. Unlike Gli1, Atoh1 cannot support GNP proliferation in the absence of Sonic Hedgehog signaling and does not govern expression of canonical cell cycle genes. Instead, Atoh1 maintains GNPs in a Sonic Hedgehog-responsive state by regulating genes that trigger neuronal differentiation, including many expressed in response to bone morphogenic protein-4. Therefore, by targeting multiple genes regulating the differentiation state of GNPs, Atoh1 collaborates with the pro-proliferative Gli1-dependent transcriptional program to influence medulloblastoma development. Keywords: disease state analysis 14 samples, 1 time series, 2 engineered Medulloblastoma tumors
2010-07-08 | E-GEOD-19684 | biostudies-arrayexpress