Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Micromanaging microRNAs: using murine models to study microRNAs in lung fibrosis.

ABSTRACT: MicroRNAs are implicated in many biological and pathological processes and are emerging as key actors in lung health and disease. Specific patterns of dysregulated microRNAs have been found in idiopathic pulmonary fibrosis (IPF), an untreatable interstitial lung disease of unknown etiology. IPF is characterized by dramatic and extensive phenotypic changes in the lung that include alveolar cell hyperplasia, fibroblast proliferation and formation of myofibroblast foci, deposition of extracellular matrix, and changes in lung transcriptional programming. Here, we discuss the latest insights about the role of microRNAs in lung fibrosis with a focus on the contribution of animal models of disease to the derivation of these insights.

SUBMITTER: Lino Cardenas CL

PROVIDER: S-EPMC4201640 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Micromanaging microRNAs: using murine models to study microRNAs in lung fibrosis.

Lino Cardenas Christian L CL Kaminski Naftali N Kass Daniel J DJ

Drug discovery today. Disease models 20130101 3

MicroRNAs are implicated in many biological and pathological processes and are emerging as key actors in lung health and disease. Specific patterns of dysregulated microRNAs have been found in idiopathic pulmonary fibrosis (IPF), an untreatable interstitial lung disease of unknown etiology. IPF is characterized by dramatic and extensive phenotypic changes in the lung that include alveolar cell hyperplasia, fibroblast proliferation and formation of myofibroblast foci, deposition of extracellular ...[more]

PMID: 25328532

Similar Datasets

MicroRNAs and micromanaging the skeleton in disease, development and evolution.

Project description:MicroRNAs (miRNAs) are short, non-protein-encoding RNAs that effect post-transcriptional gene regulation by targeting messenger RNAs. miRNAs are associated with specific human diseases and help regulate development. Here we review recent advances in understanding the roles of miRNAs in skeletal malformations, including cleft palate, and in the evolution of skeletal morphologies. We propose the hypothesis that evolutionary variation in miRNA expression patterns or structural variation in miRNA binding sites in messenger RNAs can help explain the evolution of craniofacial variation among species, the development of human craniofacial disease and physiological changes leading to osteopenia that increases with ageing.

| S-EPMC2828950 | biostudies-literature

Small-molecule-mediated OGG1 inhibition attenuates pulmonary inflammation and lung fibrosis in a murine lung fibrosis model.

Project description:Interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF) are caused by persistent micro-injuries to alveolar epithelial tissues accompanied by aberrant repair processes. IPF is currently treated with pirfenidone and nintedanib, compounds which slow the rate of disease progression but fail to target underlying pathophysiological mechanisms. The DNA repair protein 8-oxoguanine DNA glycosylase-1 (OGG1) has significant roles in the modulation of inflammation and metabolic syndromes. Currently, no pharmaceutical solutions targeting OGG1 have been utilized in the treatment of IPF. In this study we show Ogg1-targeting siRNA mitigates bleomycin-induced pulmonary fibrosis in male mice, highlighting OGG1 as a tractable target in lung fibrosis. The small molecule OGG1 inhibitor, TH5487, decreases myofibroblast transition and associated pro-fibrotic gene expressions in fibroblast cells. In addition, TH5487 decreases levels of pro-inflammatory mediators, inflammatory cell infiltration, and lung remodeling in a murine model of bleomycin-induced pulmonary fibrosis conducted in male C57BL6/J mice. OGG1 and SMAD7 interact to induce fibroblast proliferation and differentiation and display roles in fibrotic murine and IPF patient lung tissue. Taken together, these data suggest that TH5487 is a potentially clinically relevant treatment for IPF but further study in human trials is required.

| S-EPMC9902543 | biostudies-literature

Expression profile of androgen-modulated microRNAs in the fetal murine lung.

Project description:Androgens are known to delay lung development. As a consequence, the incidence and morbidity of respiratory distress syndrome of the neonate are higher for male than for female premature infants. We previously reported that many genes were expressed with a sex difference in the mouse developing lung and that several genes were under the control of androgens in the male fetal lung. microRNAs are small non-coding RNAs known to negatively regulate the expression of specific genes. In this study, we examined whether murine miRNAs are under the control of androgens in the male developing lung.Expression profiling of microRNAs was performed by microarrays using RNA extracted from male fetal lungs isolated on gestational day (GD) 17.0 and GD 18.0 after daily injection of pregnant mice from GD 10.0 with the antiandrogen flutamide or vehicle only. To identify putative miRNA target genes, the data obtained here were combined with gene profiling data reported previously using the same RNA preparations. qPCR was used to confirm microarray data with fetal lungs from other litters than those used in microarrays.Flutamide induced downregulation and upregulation of several miRNAs on GD 17.0 and GD 18.0. Of the 43 mature miRNAs modulated by flutamide on GD 17.0, 60 % were downregulated, whereas this proportion was only of 34 % for the 35 mature miRNAs modulated on GD 18.0. For 29 and 26 flutamide-responsive miRNAs, we found a corresponding target inversely regulated by androgens on GD 17.0 and 18.0, respectively. The androgen-regulated target genes were involved in several biological processes (lipid metabolism, cell proliferation, and lung development) and molecular functions, mainly transcription factor binding.Regulation of male lung development involves several miRNAs that are under androgen modulation in vivo.

| S-EPMC4818395 | biostudies-literature

Autochthonous murine models for the study of smoker and never-smoker associated lung cancers.

Project description:Lung cancer accounts for the greatest number of cancer deaths in the world. Tobacco smoke-associated cancers constitute the majority of lung cancer cases but never-smoker cancers comprise a significant and increasing fraction of cases. Recent genomic and transcriptomic sequencing efforts of lung cancers have revealed distinct sets of genetic aberrations of smoker and never-smoker lung cancers that implicate disparate biology and therapeutic strategies. Autochthonous mouse models have contributed greatly to our understanding of lung cancer biology and identified novel therapeutic targets and strategies in the era of targeted therapy. With the emergence of immuno-oncology, mouse models may continue to serve as valuable platforms for novel biological insights and therapeutic strategies. Here, we will review the variety of available autochthonous mouse models of lung cancer, their relation to human smoker and never-smoker lung cancers, and their application to immuno-oncology and immune checkpoint blockade that is revolutionizing lung cancer therapy.

| S-EPMC6131182 | biostudies-literature

Role of integrin alpha8 in murine model of lung fibrosis.

Project description:BackgroundIntegrin ?8 (ITGA8) heterodimerizes with integrin ?1 and is highly expressed in stromal cells of the lung. Platelet-derived growth factor receptor beta (PDGFR?+) cells constitute a major population of contractile myofibroblasts in the lung following bleomycin-induced fibrosis. Integrin ?8?1 is upregulated in fibrotic foci in bleomycin-induced lung injury. However, the functional role of ITGA8 in fibrogenesis has not been characterized. In this study, we examined whether genetic deletion of ITGA8 from PDGFR?+ cells in the lung altered fibrosis.MethodsPdgfrb-Cre/+;Itga8flox/- or Pdgfrb-Cre/+;Itga8flox/flox (Cre+) and control mice (Cre-) were used for in vitro and in vivo studies. Primary cultures of PDGFR?+ cells were exposed to TGF?, followed by RNA isolation for qPCR. For in vivo studies, Cre+ and Cre- mice were characterized at baseline and after bleomycin-induced fibrosis.ResultsPDGFR?-selected cells from Cre+ animals showed higher levels of Col1a1 expression after treatment with TGF?. However, Cre- and Cre+ animals showed no significant difference in measures of acute lung injury or fibrosis following bleomycin challenge.ConclusionWhile ITGA8 deletion in lung PDGFR?+ stromal cells showed evidence of greater Col1a1 mRNA expression after TGF? treatment in vitro, no functional difference was detected in vivo.

| S-EPMC5973593 | biostudies-literature

Estrogen Signaling and MicroRNAs in Lung Fibrosis. Sex, Hormones, and Rock Scars.

Project description: Not available

| S-EPMC6857495 | biostudies-literature

A Comparative Study of Lung Host Defense in Murine Obesity Models. Insights into Neutrophil Function.

Project description:We have shown that obesity-associated attenuation of murine acute lung injury is driven, in part, by blunted neutrophil chemotaxis, yet differences were noted between the two models of obesity studied. We hypothesized that obesity-associated impairment of multiple neutrophil functions contributes to increased risk for respiratory infection but that such impairments may vary between murine models of obesity. We examined the most commonly used murine obesity models (diet-induced obesity, db/db, CPE(fat/fat), and ob/ob) using a Klebsiella pneumoniae pneumonia model and LPS-induced pneumonitis. Marrow-derived neutrophils from uninjured lean and obese mice were examined for in vitro functional responses. All obesity models showed impaired clearance of K. pneumoniae, but in differing temporal patterns. Failure to contain infection in obese mice was seen in the db/db model at both 24 and 48 hours, yet this defect was only evident at 24 hours in CPE(fat/fat) and ob/ob models, and at 48 hours in diet-induced obesity. LPS-induced airspace neutrophilia was decreased in all models, and associated with blood neutropenia in the ob/ob model but with leukocytosis in the others. Obese mouse neutrophils from all models demonstrated impaired chemotaxis, whereas neutrophil granulocyte colony-stimulating factor-mediated survival, LPS-induced cytokine transcription, and mitogen-activated protein kinase and signal transducer and activator of transcription 3 activation in response to LPS and granulocyte colony-stimulating factor, respectively, were variably impaired across the four models. Obesity-associated impairment of host response to lung infection is characterized by defects in neutrophil recruitment and survival. However, critical differences exist between commonly used mouse models of obesity and may reflect variable penetrance of elements of the metabolic syndrome, as well as other factors.

| S-EPMC4979371 | biostudies-literature

Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models.

Project description:Hepatic fibrosis, featured by the accumulation of excessive extracellular matrix in liver tissue, is associated with metabolic disease and cancer. Inhalation exposure to airborne particulate matter in fine ranges (PM2.5) correlates with pulmonary dysfunction, cardiovascular disease, and metabolic syndrome. In this study, we investigated the effect and mechanism of PM2.5 exposure on hepatic fibrogenesis.Both inhalation exposure of mice and in vitro exposure of specialized cells to PM2.5 were performed to elucidate the effect of PM2.5 exposure on hepatic fibrosis. Histological examinations, gene expression analyses, and genetic animal models were utilized to determine the effect and mechanism by which PM2.5 exposure promotes hepatic fibrosis.Inhalation exposure to concentrated ambient PM2.5 induces hepatic fibrosis in mice under the normal chow or high-fat diet. Mice after PM2.5 exposure displayed increased expression of collagens in liver tissues. Exposure to PM2.5 led to activation of the transforming growth factor ?-SMAD3 signaling, suppression of peroxisome proliferator-activated receptor ?, and expression of collagens in hepatic stellate cells. NADPH oxidase plays a critical role in PM2.5-induced liver fibrogenesis.Exposure to PM2.5 exerts discernible effects on promoting hepatic fibrogenesis. NADPH oxidase mediates the effects of PM2.5 exposure on promoting hepatic fibrosis.

| S-EPMC5003300 | biostudies-literature

MicroRNAs as theranostic markers in cardiac allograft transplantation: from murine models to clinical practice.

Project description:Congestive heart failure affects about 23 million people worldwide, and cardiac allograft transplantation remains one of the last options for patients with terminal refractory heart failure. Besides the infectious or oncological complications, the prognosis of patients after heart transplantation is affected by acute cellular or antibody-mediated rejection and allograft vasculopathy development. Current monitoring of both conditions requires the performance of invasive procedures (endomyocardial biopsy sampling and coronary angiography or optical coherence tomography, respectively) that are costly, time-demanding, and non-comfortable for the patient. Within this narrative review, we focus on the potential pathophysiological and clinical roles of microRNAs (miRNAs, miRs) in the field of cardiac allograft transplantation. Firstly, we provide a general introduction about the status of cardiac allograft function monitoring and the discovery of miRNAs as post-transcriptional regulators of gene expression and clinically relevant biomarkers found in the extracellular fluid. After this general introduction, information from animal and human studies are summarized to underline the importance of miRNAs both in the pathophysiology of the rejection process, the possibility of its modulation by altering miRNAs levels, and last but not least, about the use of miRNAs in the clinical practice to diagnose or predict the rejection occurrence.

| S-EPMC8058726 | biostudies-literature

Endoglin in human liver disease and murine models of liver fibrosis-A protective factor against liver fibrosis.

Project description:Background & aimsLiver fibrosis is the outcome of chronic liver injury. Transforming growth factor-? (TGF-?) is a major profibrogenic cytokine modulating hepatic stellate cell (HSC) activation and extracellular matrix homeostasis. This study analyses the effect of Endoglin (Eng), a TGF-? type III auxiliary receptor, on fibrogenesis in two models of liver injury by HSC-specific endoglin deletion.MethodsEng expression was measured in human and murine samples of liver injury. After generating GFAPCre(+) Eng?HSC mice, the impact of Endoglin deletion on chronic liver fibrosis was analysed. For in vitro analysis, Engflox/flox HSCs were infected with Cre-expressing virus to deplete Endoglin and fibrogenic responses were analysed.ResultsEndoglin is upregulated in human liver injury. The receptor is expressed in liver tissues and mesenchymal liver cells with much higher abundance of the L-Eng splice variant. Comparing GFAPCre(-) Engf/f to GFAPCre(+) Eng?HSC mice in toxic liver injury, livers of GFAPCre(+) Eng?HSC mice showed 39.9% (P < .01) higher Hydroxyproline content compared to GFAPCre(-) Engf/f littermates. Sirius Red staining underlined these findings, showing 58.8% (P < .05) more Collagen deposition in livers of GFAPCre(+) Eng?HSC mice. Similar results were obtained in mice subjected to cholestatic injury.ConclusionEndoglin isoforms are differentially upregulated in liver samples of patients with chronic and acute liver injury. Endoglin deficiency in HSC significantly aggravates fibrosis in response to injury in two different murine models of liver fibrosis and increases ?-SMA and fibronectin expression in vitro. This suggests that Endoglin protects against fibrotic injury, likely through modulation of TGF-? signalling.

| S-EPMC5947658 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data