MircroRNA-92b, a Novel Negative Regulator of the Transforming Growth Factor-β Signaling Pathway Targeting the Type I Receptor
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1013053 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25916502_1.fastq.gz | Fastqsanger.gz | |||
| SRR25916502_2.fastq.gz | Fastqsanger.gz | |||
| SRR25916503_1.fastq.gz | Fastqsanger.gz | |||
| SRR25916503_2.fastq.gz | Fastqsanger.gz | |||
| SRR25916504_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Progressive renal disease is the consequence of destructive fibrosis. Renal fibrosis is a common outcome of many chronic kidney diseases, including diabetic kidney disease (DKD). Transforming growth factor-β1 (TGFβ1) has been identified as a major pathogenic factor underlying the development of DKD. It had been reported that the expression of miR-92b-3p had been reported to be reduced in the kidneys from diabetic mice and patients with DKD. However, the role of miR-92b-3p in the progress of renal fibrosis was remaining largely unknown. This study investigated the role of miR-92b-3p in the progression of renal fibrosis in unilateral ureteral occlusion (UUO) and unilateral ischemia-reperfusion injury (uIRI) mouse models, as well as explored its underlying mechanisms in human proximal tubular epithelial (HK2) cells. We found that renal fibrosis increased in UUO mice after miR-92b knockout, while reduced in miR-92b overexpressing mice. MiR-92b knockout aggravated renal fibrosis in unilateral ischemia-reperfusion injury. RNA-sequencing analysis, the luciferase reporter assay, qPCR analysis, and western blotting confirmed that miR-92b-3p directly targeted TGF-β receptor 1 (TGFBR1), thereby ameliorating renal fibrosis by suppressing the TGF-β/SMAD3 signaling pathway. Furthermore, we found that TGF-β suppressed miR-92b transcription through Snail family transcriptional repressors 1 (SNAI1) and SNAI2. Our results suggest that miR-92b-3p may serve as a novel therapeutic for mitigating fibrosis in chronic kidney disease.
2023-10-01 | GSE242295 | GEO
Project description:The transforming growth factor-ss (TGF-beta) signaling pathway plays a pivotal role in diverse cellular processes. TGF-beta switches its role from a tumor suppressor in normal or dysplastic cells to a tumor promoter in advanced cancers. It is widely believed that the Smad-dependent pathway is involved in TGF-beta tumor-suppressive functions, whereas activation of Smad-independent pathways, coupled with the loss of tumor-suppressor functions of TGF-beta, is important for its pro-oncogenic functions. TGF-beta signaling has been considered a useful therapeutic target. The discovery of oncogenic actions of TGF-beta has generated a great deal of enthusiasm for developing TGF-beta signaling inhibitors for the treatment of cancer. The challenge is to identify the group of patients where targeted tumors are not only refractory to TGF-beta-induced tumor suppressor functions but also responsive to the tumor-promoting effects of TGF-beta. TGF-beta pathway inhibitors, including small and large molecules, have now entered clinical trials. Preclinical studies with these inhibitors have shown promise in a variety of different tumor models. Here, we focus on the mechanisms of signaling and specific targets of the TGF-beta pathway that are critical effectors of tumor progression and invasion. This report also examines the therapeutic intervention of TGF-ss signaling in human cancers.
| S-EPMC2796203 | biostudies-literature
Project description:BackgroundVascular smooth muscle cells (SMCs) synthesize extracellular matrix (ECM) that contributes to tissue remodeling after revascularization interventions. The cytokine transforming growth factor β (TGF-β) is induced on tissue injury and regulates tissue remodeling and wound healing, but dysregulated signaling results in excess ECM deposition and fibrosis. The LIM (Lin11, Isl-1 & Mec-3) domain protein LIM domain only 7 (LMO7) is a TGF-β1 target gene in hepatoma cells, but its role in vascular physiology and fibrosis is unknown.MethodsWe use carotid ligation and femoral artery denudation models in mice with global or inducible smooth muscle-specific deletion of LMO7, and knockout, knockdown, overexpression, and mutagenesis approaches in mouse and human SMC, and human arteriovenous fistula and cardiac allograft vasculopathy samples to assess the role of LMO7 in neointima and fibrosis.ResultsWe demonstrate that LMO7 is induced postinjury and by TGF-β in SMC in vitro. Global or SMC-specific LMO7 deletion enhanced neointimal formation, TGF-β signaling, ECM deposition, and proliferation in vascular injury models. LMO7 loss of function in human and mouse SMC enhanced ECM protein expression at baseline and after TGF-β treatment. TGF-β neutralization or receptor antagonism prevented the exacerbated neointimal formation and ECM synthesis conferred by loss of LMO7. Notably, loss of LMO7 coordinately amplified TGF-β signaling by inducing expression of Tgfb1 mRNA, TGF-β protein, αv and β3 integrins that promote activation of latent TGF-β, and downstream effectors SMAD3 phosphorylation and connective tissue growth factor. Mechanistically, the LMO7 LIM domain interacts with activator protein 1 transcription factor subunits c-FOS and c-JUN and promotes their ubiquitination and degradation, disrupting activator protein 1-dependent TGF-β autoinduction. Importantly, preliminary studies suggest that LMO7 is upregulated in human intimal hyperplastic arteriovenous fistula and cardiac allograft vasculopathy samples, and inversely correlates with SMAD3 phosphorylation in cardiac allograft vasculopathy.ConclusionsLMO7 is induced by TGF-β and serves to limit vascular fibrotic responses through negative feedback regulation of the TGF-β pathway. This mechanism has important implications for intimal hyperplasia, wound healing, and fibrotic diseases.
| S-EPMC6371979 | biostudies-literature
Project description:Transforming growth factor (TGF-β) is a multifunctional cytokine that plays essential roles in regulating mammary gland development, morphogenesis, differentiation, and involution. TGF-β also regulates mammary gland homeostasis and prevents its transformation by prohibiting dysregulated cell cycle progression, and by inducing apoptosis; it also creates cell microenvironments that readily inhibit cell migration, invasion, and metastasis. Interestingly, while early-stage mammary tumors remain sensitive to the tumor suppressing activities of TGF-β, late-stage breast cancers become insensitive to the anticancer functions of this cytokine and instead rely upon TGF-β to drive disease and metastatic progression. This switch in TGF-β function is known as the "TGF-β Paradox" and represents the rationale for developing chemotherapies to inactivate the TGF-β pathway and its oncogenic functions in late-stage breast cancers. Here we outline the molecular mechanisms that manifest the "TGF-β Paradox" and discuss the challenges associated with the development and use of anti-TGF-β agents to treat breast cancer patients.
| S-EPMC4403665 | biostudies-literature
Project description:total RNA from mouse (male c57BL/6) spleen labeled with Cy3 vs total RNA from mouse (male c57BL/6) B cells treated with TGF-beta (transforming growth factor-beta) labeled with Cy5- time course with repeats Keywords: ordered
2003-04-14 | GSE400 | GEO
Project description:Fibrosis affects an extensive range of organs and is increasingly acknowledged as a major component of many chronic disorders. It is now well accepted that the elevated expression of certain inflammatory cell-derived cytokines, especially transforming growth factor β (TGFβ), is involved in the epithelial-to-mesenchymal transition (EMT) leading to the pathogenesis of a diverse range of fibrotic diseases. In lens, aberrant TGFβ signaling has been shown to induce EMT leading to cataract formation. Sproutys (Sprys) are negative feedback regulators of receptor tyrosine kinase (RTK)-signaling pathways in many vertebrate systems, and in this study we showed that they are important in the murine lens for promoting the lens epithelial cell phenotype. Conditional deletion of Spry1 and Spry2 specifically from the lens leads to an aberrant increase in RTK-mediated extracellular signal-regulated kinase 1/2 phosphorylation and, surprisingly, elevated TGFβ-related signaling in lens epithelial cells, leading to an EMT and subsequent cataract formation. Conversely, increased Spry overexpression in lens cells can suppress not only TGFβ-induced signaling, but also the accompanying EMT and cataract formation. On the basis of these findings, we propose that a better understanding of the relationship between Spry and TGFβ signaling will not only elucidate the etiology of lens pathology, but will also lead to the development of treatments for other fibrotic-related diseases associated with TGFβ-induced EMT.
| S-EPMC3409273 | biostudies-literature
Project description:Hypertrophic scar (HPS) presents as excessive extracellular matrix deposition and abnormal function of fibroblasts. However, there is no single satisfactory method to prevent HPS formation so far. Here, we found that honokiol (HKL), a natural compound isolated from Magnolia tree, had an inhibitory effect on HPS both in vitro and in vivo. Firstly, HKL could dose-dependently down-regulate the mRNA and protein levels of type I collagen, type III collagen, and α-smooth muscle actin (α-SMA) in hypertrophic scar-derived fibroblasts (HSFs). Secondly, HKL suppressed the proliferation, migration abilities of HSFs and inhibited HSFs activation to myofibroblasts, but had no effect on cell apoptosis. Besides, the in vivo rabbit ear scar model further affirmed the inhibitory effects of HKL on collagen deposition, proliferating cell nuclear antigen and α-SMA. Finally, Western blot results showed that HKL reduced the phosphorylation status of Smad2/3, as well as affected the protein levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase1. Taken together, this study demonstrated that HKL alleviated HPS by suppressing fibrosis-related molecules and inhibiting HSFs proliferation, migration as well as activation to myofibroblasts via Smad-dependent pathway. Therefore, HKL could be used as a potential agent for treating HPS and other fibrotic diseases.
| S-EPMC5395562 | biostudies-literature
Project description:We have examined the changes in gene expression aftert reatment of A549 cells, a cultured alveolar epithelial cells, with flagellin and transforming growth factor beta 1. In this dataset, we include the expression data obtained from A549 cells after treatment with purified flagellin or transforming growth factor beta 1 receptor. The analysis indicated that flagellin induced a change in gene expression that was similar to the changes induced by transforming growth factor 1. A549 cells were treated with flagellin or transforming growth factor 1 for 24 h. Total RNA was extracted and reverse transcribed to cDNA. Synthesized cDNA was fragmented and labeled with biotin. The biotinylated cDNA was hybridized to to an Affymetrix GeneChip Array, and probe signal intensities were captured.
2012-10-31 | E-GEOD-38309 | biostudies-arrayexpress
Project description:Most cancers are characterized by excessive transforming growth factor-beta production by tumors, which can promote tumor growth and mediate epithelial-to-mesenchymal transition. Transforming growth factor-beta also has the ability to overproduce extracellular matrix components in response to injury and other stimuli. There are many strategies undergoing current evaluation for inhibiting the deleterious biological effects of transforming growth factor-beta by disrupting its signaling at various levels. The current review focuses on the recent advances made in this area, and the potential of these strategies in the clinical treatment of cancer and fibrosis.Four main strategies used most recently for disrupting transforming growth factor-beta signaling are brought into focus in this review: inhibition or sequestration of the transforming growth factor-beta protein ligands, inhibition of transforming growth factor-beta receptor kinase activity, inhibition of SMAD signaling downstream of transforming growth factor-beta kinase activity and restoration of antitumor immunity upon transforming growth factor-beta inhibition. Various techniques currently used to employ these four strategies are discussed.Several lines of evidence suggest that altered transforming growth factor-beta signaling contributes to tumor progression and metastasis as well as development of fibrosis. Accumulating data from preclinical and clinical studies indicate that antagonizing aberrant transforming growth factor-beta signaling is a promising novel therapeutic approach in cancer and fibrotic disorders.
| S-EPMC2640227 | biostudies-other
Project description:Transforming growth factor-β (TGF-β) was originally identified as an anti-tumour cytokine. However, there is increasing evidence that it has important roles in the tumour microenvironment (TME) in facilitating cancer progression. TGF-β actively shapes the TME via modulating the host immunity. These actions are highly cell-type specific and complicated, involving both canonical and non-canonical pathways. In this review, we systemically update how TGF-β signalling acts as a checkpoint regulator for cancer immunomodulation. A better appreciation of the underlying pathogenic mechanisms at the molecular level can lead to the discovery of novel and more effective therapeutic strategies for cancer.
| S-EPMC7690808 | biostudies-literature