ASIC3-M-CSF-M2 macrophage-positive feedback loop modulates in skin fibrosis pathogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA775894 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16609136_1.fastq.gz | Fastqsanger.gz | |||
| SRR16609136_2.fastq.gz | Fastqsanger.gz | |||
| SRR16609137_1.fastq.gz | Fastqsanger.gz | |||
| SRR16609137_2.fastq.gz | Fastqsanger.gz | |||
| SRR16609138_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:Inflammation is one of the main pathological features leading to skin fibrosis and a key factor leading to the progression of skin fibrosis. Acidosis caused by a decrease in extracellular pH is a sign of the inflammatory process. Acid-sensing ion channels (ASICs) are ligand-gated ion channels on the cell membrane that sense the drop in extracellular pH. However, the molecular mechanisms by which skin fibroblasts are regulated by Acid-sensing ion channel 3(ASIC3) remain unknown. This study investigated whether ASIC3 is related to inflammation and skin fibrosis and explored the underlying mechanisms. We demonstrate that Macrophage colony-stimulating factor (M-CSF) is a direct target of ASIC3, and ASIC3 activation promotes M-CSF transcriptional regulation of macrophages for M2 polarization. The polarization of M2 macrophages transduced by the ASIC3-M-CSF signal promotes the differentiation of fibroblasts into myofibroblasts through transforming growth factor β1 (TGF-β1), thereby producing ASIC3-M-CSF-TGF-β1 positive feedback loop. Targeting ASIC3 may be a new treatment strategy for skin fibrosis.
2021-10-30 | GSE186739 | GEO
Project description:Inflammation is one of the main pathological features leading to skin fibrosis and a key factor leading to the progression of skin fibrosis. Acidosis caused by a decrease in extracellular pH is a sign of the inflammatory process. Acid-sensing ion channels (ASICs) are ligand-gated ion channels on the cell membrane that sense the drop in extracellular pH. The molecular mechanisms by which skin fibroblasts are regulated by acid-sensing ion channel 3 (ASIC3) remain unknown. This study investigated whether ASIC3 is related to inflammation and skin fibrosis and explored the underlying mechanisms. We demonstrate that macrophage colony-stimulating factor (M-CSF) is a direct target of ASIC3, and ASIC3 activation promotes M-CSF transcriptional regulation of macrophages for M2 polarization. The polarization of M2 macrophages transduced by the ASIC3-M-CSF signal promotes the differentiation of fibroblasts into myofibroblasts through transforming growth factor β1 (TGF-β1), thereby producing an ASIC3-M-CSF-TGF-β1 positive feedback loop. Targeting ASIC3 may be a new treatment strategy for skin fibrosis.
| S-EPMC9167818 | biostudies-literature
Project description:Analyses of RNAi-heterochromatin positive feedback loop in Tetrahymena
| PRJNA343227 | ENA
Project description:Successful infection strategies must balance pathogen amplification and persistence. In Toxoplasma gondii, this is accomplished through differentiation into dedicated cyst-forming chronic stages that avoid clearance by the host immune system. The transcription factor BFD1 is both necessary and sufficient for stage conversion; however, its regulation is not understood. We examine five factors transcriptionally activated by BFD1. One of these is a cytosolic RNA-binding protein of the CCCH-type zinc finger family, which we name BFD2. Parasites lacking BFD2 fail to induce BFD1 and are consequently unable to fully differentiate in culture or in mice. BFD2 interacts with the BFD1 transcript under stress and deletion of BFD2 reduces BFD1 protein levels, but not mRNA abundance. The reciprocal effects on BFD2 transcription and BFD1 translation outline a positive feedback loop that enforces commitment to differentiation. BFD2 helps explain how parasites commit to the chronic gene-expression program and elucidates how the balance between proliferation and persistence is achieved over the course of infection.
2023-08-07 | PXD039648 | Pride
Project description:Aberrant glucose metabolism is a characteristic of bladder cancer. Hyperglycemia contributes to the development and progression of bladder cancer. However, the underlying mechanism by which hyperglycemia promotes the aggressiveness of cancers, especially bladder cancer, is still incompletely understood. N6-methyladenosine (m6A) modification is a kind of methylation modification occurring at the N6 position of adenosine that is important for the pathogenesis of urological tumors. Recently, it was found that the m6A reader YTHDC1 is regulated by high-glucose conditions. In our study, we revealed that YTHDC1 is not only regulated by high-glucose conditions but is also downregulated in bladder cancer tissue and associated with the prognosis of cancer. We also showed that YTHDC1 suppresses the malignant progression of and the glycolytic process in bladder cancer cells in an m6A-dependent manner and determined that this effect is partially mediated by GLUT3. Moreover, GLUT3 was found to destabilize YTHDC1 by upregulating RNF183 expression. In summary, we identified a novel YTHDC1/GLUT3/RNF183 feedback loop that regulates disease progression and glucose metabolism in bladder cancer. Collectively, this study provides new insight regarding the pathogenesis of bladder cancer under hyperglycemic conditions and might reveal ideal candidates for the development of drugs for bladder cancer.
2025-03-10 | GSE291591 | GEO
Project description:Fundamental processes of obligate intracellular parasites, such as Plasmodium falciparum and Toxoplasma gondii are controlled by a set of plant-like calcium dependent kinases (CDPKs), the conserved cAMP- and cGMP-dependent protein kinases (PKA and PKG), second messengers and lipid signalling. While some major components of the signalling networks have been identified, how these are connected is largely not known. Here, we compare the phospho-signalling networks during Toxoplasma egress from its host cell by artificially raising cGMP or calcium levels to activate PKG or CDPKs, respectively. We show that both these inducers trigger near identical signalling pathways and provide evidence for a feedback loop involving CDPK3. We measure phospho- and lipid signalling in parasites treated with the Ca2+ ionophore A23187 in a sub-minute timecourse and show CDPK3-dependent regulation of diacylglycerol levels and increased phosphorylation of four phosphodiesterases (PDEs), suggesting their function in the feedback loop. Disruption of CDPK3 leads to elevated cAMP levels and inhibition of PKA signalling rescues the egress defect of ΔCDPK3 parasites treated with A23187. Biochemical analysis of the four PDEs identifies PDE2 as the only cAMP-specific PDE among these candidates while the other PDEs are cGMP specific; two of which are inhibited by the predicted PDE inhibitor BIPPO. Conditional deletion of the 4 PDEs supports an important, but non-essential role of PDE1 and PDE2 for growth, while only the latter plays a role in controlling A23187-mediated egress. In summary, we uncover a positive feedback loop that potentiates signalling during egress and links several signalling pathways together.
2022-10-17 | PXD030057 | Pride
Project description:Here we screened and identified a novel oncogenic lncRNA, ZNF252P, which is upregulated in a variety of cancer types. ZNF252P promotes cancer cell proliferation and tumorigenicity in vitro and in vivo by activating c-Myc-mediated positive feedback loop. The pivotal regulatory axis of ZNF252P/c-Myc gives it the potential to be the promising biomarker and therapeutic target in cancer development.
2025-01-21 | GSE271524 | GEO
Project description:ZNF252P promotes tumorigenesis by activating c-Myc-mediated positive feedback loop
| PRJNA1132162 | ENA
Project description:In the ciliated protozoan Tetrahymena, an RNAi-mediated feedback loop is important for assembling heterochromatin on the sequences that are removed from the somatic genome by programmed DNA elimination. Because heterochromatin is formed exclusively on the eliminated sequences, some mechanism must inhibit this feedback loop at the boundaries of the eliminated sequences. In this study, we show that the HP1-like protein Coi6p, its interaction partners Coi7p and Lia5p, and the histone demethylase Jmj1p are crucial for confining the production of small RNAs to the eliminated sequences.
2017-03-06 | GSE87011 | GEO
Project description:Keratinocyte skin cancer, comprising cutaneous squamous (cSCC) and basal cell carcinoma, is the most common malignancy in the UK. P53 is frequently mutated in cSCC. iASPP is a key inhibitor of p53 and NF-kB signalling pathways and has been documented as highly expressed in several types of human cancer. We have previously identified an autoregulatory feedback loop between iASPP and p63, which is critical in epidermal homeostasis. We hypothesised a potential role for dysregulation of this axis in the pathogenesis of keratinocyte malignancies. Immunostaining of 116 cSCC clinical samples revealed increased iASPP and ΔNp63 expression but also highlighted a significant alteration of iASPP cellular localisation, with consequent deregulation of its function. Expression patterns, functionality, gene and microRNA expression analysis were further investigated in 10 cSCC cell lines. Our data suggest that whilst direct effects of iASPP and p63 upon each other’s expression are maintained in cSCC, epigenetic dysregulation of the feedback loop occurs at the microRNA level by a novel mechanism controlling p63 expression. We demonstrate that this autoregulatory feedback loop controls cell migration in cSCC by blocking EMT and promoting proliferation, and provides future directions for clinical biomarker and therapeutic target discovery in cutaneous SCC.
2019-11-20 | GSE123189 | GEO