Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pharmacological Inhibition of TAK1 Prevents and Induces Regression of fibrosis

ABSTRACT: Pharmacological Inhibition of TAK1 Prevents and Induces Regression of fibrosis

PROVIDER: PRJNA971977 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR24525376_1.fastq.gz	Fastqsanger.gz
	SRR24525376_2.fastq.gz	Fastqsanger.gz
	SRR24525377_1.fastq.gz	Fastqsanger.gz
	SRR24525377_2.fastq.gz	Fastqsanger.gz
	SRR24525378_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 18

Similar Datasets

Pharmacological Inhibition of TAK1 Prevents and Induces Regression of fibrosis

Project description:To evaluate the effects of TAK1 inhibition on TGF-beta regulated fibrosis using a novel small molecule inhibitor of TAK1.

2023-05-17 | GSE232435 | GEO

Pharmacological inhibition of TAK1 prevents and induces regression of experimental organ fibrosis.

Project description:Multiorgan fibrosis in systemic sclerosis (SSc) accounts for substantial mortality and lacks effective therapies. Lying at the crossroad of TGF-β and TLR signaling, TGF-β-activated kinase 1 (TAK1) might have a pathogenic role in SSc. We therefore sought to evaluate the TAK1 signaling axis in patients with SSc and to investigate pharmacological TAK1 blockade using a potentially novel drug-like selective TAK1 inhibitor, HS-276. Inhibiting TAK1 abrogated TGF-β1 stimulation of collagen synthesis and myofibroblasts differentiation in healthy skin fibroblasts, and it ameliorated constitutive activation of SSc skin fibroblasts. Moreover, treatment with HS-276 prevented dermal and pulmonary fibrosis and reduced the expression of profibrotic mediators in bleomycin-treated mice. Importantly, initiating HS-276 treatment even after fibrosis was already established prevented its progression in affected organs. Together, these findings implicate TAK1 in the pathogenesis of SSc and identify targeted TAK1 inhibition using a small molecule as a potential strategy for the treatment of SSc and other fibrotic diseases.

| S-EPMC10443806 | biostudies-literature

Hepatocyte-Specific TAK1 Deficiency Drives RIPK1 Kinase-dependent Inflammation to Promote Liver Fibrosis and Hepatocellular Carcinoma

Project description:Transforming growth factor beta-activated kinase1 (TAK1) encoded by the gene MAP3K7 regulates multiple important downstream effectors involved in immune response, cell death and carcinogenesis. Hepatocyte-specific deletion of TAK1 in Tak1_Hep mice promotes liver fibrosis and hepatocellular carcinoma (HCC) formation. Here, we report that genetic inactivation of RIPK1 kinase using kinase dead knock-in D138N mutation in Tak1_Hep mice inhibits the expression of liver tumor biomarkers, liver fibrosis and HCC formation. Inhibition of RIPK1, however, has no or minimum effect on hepatocyte loss and compensatory proliferation, which are the recognized factors important for liver fibrosis and HCC development. Using single cell RNA-seq, we discover that inhibition of RIPK1 strongly suppresses inflammation induced by hepatocyte-specific loss of TAK1. Activation of RIPK1 promotes the transcription of key proinflammatory cytokines, such as CCL2, and CCR2+ macrophage infiltration. Our study demonstrates the role and mechanism of RIPK1 kinase in promoting inflammation, both cell-autonomously and cell-non-autonomously, in the development of liver fibrosis and HCC, independent of cell death and compensatory proliferation. We suggest the possibility of inhibiting RIPK1 kinase as a therapeutic strategy for reducing liver fibrosis and HCC development by inhibiting inflammation.

2020-07-08 | GSE148859 | GEO

Lipid Associated Macrophages' Promotion of Fibrosis Resolution during MASH regression requires TREM2

Project description:While macrophage heterogeneity during Metabolic dysfunction-associated steatohepatitis (MASH) has been described, the fate of these macrophages during MASH regression is poorly understood. Comparing macrophage heterogeneity during MASH progression vs regression, we identified specific macrophage sub- populations that are critical for MASH/fibrosis resolution. We elucidated the restorative pathways and gene signatures that define regression associated macrophages (RAM) and establish the importance of TREM2+ macrophages during MASH regression. Liver resident Kupffer cells are lost during MASH and are replaced by four distinct monocyte derived macrophage sub-populations. Trem2 is expressed in two macrophage sub- populations: (i) monocyte-derived macrophages occupying the Kupffer cell niche (MoKC) and (ii) lipid-associated macrophages (LAM). In regression livers, no new transcriptionally distinct MF sub-population emerged. However, the relative macrophage composition changed during regression compared to MASH. While MoKC was the major macrophage sub-population during MASH, they decreased during regression. LAM was the dominant macrophage sub-type during MASH regression and maintained Trem2 expression. Both MoKC and LAM were enriched in disease resolving pathways. Absence of TREM2 restricted the emergence of LAMs and formation of hepatic crown like structures (hCLS). TREM2+ macrophages are functionally important not only for restricting MASH-fibrosis progression, but also for effective regression of inflammation and fibrosis. TREM2+ MF are superior collagen degraders. Lack of TREM2+ macrophages also prevented elimination of hepatic steatosis and inactivation of HSC during regression, indicating their significance in metabolic co-ordination with other cell- types in the liver. TREM2 imparts this protective effect through multifactorial mechanisms, including improved phagocytosis, lipid-handling and collagen degradation.

2024-08-05 | GSE261829 | GEO

Blocking MAIT cell activation can modulate macrophage gene signature during liver fibrosis regression

Project description:Exploratory RNA sequencing of pro-inflammatory (Ly6C high) and resolutive (Ly6C low) macrophages in mouse liver during fibrosis regression. Mice were treated with a MAIT antagonist or its control vehicle for 2 days after the last CCl4 injection. Ly6C high and Ly6C low macrophages were sorted by ARIA III.

2023-02-10 | GSE183906 | GEO

Pharmacological inhibition of lipolysis prevents adverse metabolic outcomes during glucocorticoid administration

Project description:Pharmacological inhibition of lipolysis prevents adverse metabolic outcomes during glucocorticoid administration

| PRJNA939555 | ENA

Deubiquitinase USP29 Ameliorates Pathological Cardiac Hypertrophy Through Inhibiting TAK1

Project description:The identification of key factors involved in pathological cardiac hypertrophy is crucial to exploring novel treatments for heart failure. In this study, we elucidated the role of Ubiquitin-specific protease 29 (USP29), a deubiquitinase, in pressure overload-induced cardiac hypertrophy. Genetic knockout of USP29 in mice significantly exacerbated TAC-induced heart hypertrophy, dysfunction, and fibrosis; whereas overexpression of USP29 in cardiomyocytes attenuated the hypertrophic response. Similarly, USP29 markedly alleviated PE-induced hypertrophy of primary neonatal rat cardiomyocytes. Mechanistically, the cardio-protective effects mediated by USP29 were attributed to its suppression of transforming growth factor β-activated kinase 1 (TAK1)-JNK/P38 signaling pathway activation. Collectively, our study suggests that targeting either USP29 or its interaction with TAK1 could represent an innovative therapeutic strategy for treating heart failure and cardiac hypertrophy.

2024-04-20 | GSE263965 | GEO

Lipid Associated Macrophages' Promotion of Fibrosis Resolution during MASH regression requires TREM2

Project description:Lipid Associated Macrophages' Promotion of Fibrosis Resolution during MASH regression requires TREM2

| PRJNA1089178 | ENA

TAK1 is essential for growth and maintenance of skeletal muscle mass

Project description:Our results demonstrate that targeted deletion of TAK1 inhibits muscle growth during post-natal development period. Inactivation of TAK1 also causes muscle wasting in adult mice. TAK1 regulates expression of a number of molecules and signaling pathways which mediate growth and maintenance of skeletal muscle.

2018-02-28 | GSE104586 | GEO

Siglecf Deficiency Prevents Fibrosis After Bleomycin-Induced Acute Lung Injury

Project description:Siglecf Deficiency Prevents Fibrosis After Bleomycin-Induced Acute Lung Injury

| PRJNA1180106 | ENA