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Signaling modality within gp130 receptor enhances tissue regeneration [R805 treatment]

ABSTRACT: Signaling modality within gp130 receptor enhances tissue regeneration [R805 treatment]

PROVIDER: PRJNA787630 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17189083.fastq.gz	Fastqsanger.gz
	SRR17189084.fastq.gz	Fastqsanger.gz
	SRR17189085.fastq.gz	Fastqsanger.gz
	SRR17189086.fastq.gz	Fastqsanger.gz

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Signaling modality within gp130 receptor enhances tissue regeneration

Project description:Signaling modality within gp130 receptor enhances tissue regeneration

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Signaling modality within gp130 receptor enhances tissue regeneration (bulkRNA-seq)

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Signaling modality within gp130 receptor enhances tissue regeneration (Canine scRNA-seq)

Project description:Signaling modality within gp130 receptor enhances tissue regeneration (Canine scRNA-seq)

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Signaling modality within gp130 receptor enhances tissue regeneration [WT vs Y814]

Project description:Signaling modality within gp130 receptor enhances tissue regeneration [WT vs Y814]

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Signaling modality within gp130 receptor enhances tissue regeneration [R805 treatment]

Project description:Adult mammals are incapable of multi-tissue regeneration and augmentation of this potential may drastically shift current therapeutic paradigms. Here, we found that a common co-receptor of IL-6 cytokines, glycoprotein 130 (gp130), serves as a major nexus integrating various context-specific signaling inputs to either promote regenerative outcomes or aggravate disease progression. Via genetic and pharmacological experiments in vitro and in vivo, we demonstrated that a signaling tyrosine 814 (Y814) within gp130 serves as a major cellular stress sensor. Mice with constitutively inactivated Y814 (F814) exhibit regenerative, not reparative, responses after wounding in skin and anti-degenerative responses in the synovial joint. In addition, pharmacological inhibition of gp130 Y814 results in regeneration of multiple tissues in several species as well as disease modification in animal models of osteoarthritis. Our study characterizes a novel molecular mechanism that, if selectively manipulated, enhances the intrinsic regenerative capacity while preventing pathological outcomes in injury and disease.

2024-01-24 | GSE190602 | GEO

Signaling modality within gp130 receptor enhances tissue regeneration (bulkRNA-seq)

2024-01-24 | GSE168279 | GEO

Signaling modality within gp130 receptor enhances tissue regeneration [WT vs Y814]

2024-01-24 | GSE190608 | GEO

Signaling modality within gp130 receptor enhances tissue regeneration (Canine scRNA-seq)

2024-01-24 | GSE168338 | GEO

Signaling modality within gp130 receptor enhances tissue regeneration

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-01-24 | GSE168395 | GEO

Inhibition of a signaling modality within the gp130 receptor enhances tissue regeneration and mitigates osteoarthritis.

Project description:Adult mammals are incapable of multitissue regeneration, and augmentation of this potential may shift current therapeutic paradigms. We found that a common co-receptor of interleukin 6 (IL-6) cytokines, glycoprotein 130 (gp130), serves as a major nexus integrating various context-specific signaling inputs to either promote regenerative outcomes or aggravate disease progression. Via genetic and pharmacological experiments in vitro and in vivo, we demonstrated that a signaling tyrosine 814 (Y814) within gp130 serves as a major cellular stress sensor. Mice with constitutively inactivated Y814 (F814) were resistant to surgically induced osteoarthritis as reflected by reduced loss of proteoglycans, reduced synovitis, and synovial fibrosis. The F814 mice also exhibited enhanced regenerative, not reparative, responses after wounding in the skin. In addition, pharmacological modulation of gp130 Y814 upstream of the SRC and MAPK circuit by a small molecule, R805, elicited a protective effect on tissues after injury. Topical administration of R805 on mouse skin wounds resulted in enhanced hair follicle neogenesis and dermal regeneration. Intra-articular administration of R805 to rats after medial meniscal tear and to canines after arthroscopic meniscal release markedly mitigated the appearance of osteoarthritis. Single-cell sequencing data demonstrated that genetic and pharmacological modulation of Y814 resulted in attenuation of inflammatory gene signature as visualized by the anti-inflammatory macrophage and nonpathological fibroblast subpopulations in the skin and joint tissue after injury. Together, our study characterized a molecular mechanism that, if manipulated, enhances the intrinsic regenerative capacity of tissues through suppression of a proinflammatory milieu and prevents pathological outcomes in injury and disease.

| S-EPMC10792550 | biostudies-literature

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