Molecular Mechanisms of Antifibrotic Effect of Interferon Gamma in Bleomycin-Mouse Model of Lung Fibrosis: Downregulation of TGF-β and Procollagen I and III Gene Expression

1995 ◽  
Vol 21 (5) ◽  
pp. 791-808 ◽  
Author(s):  
G. Gurujeyalakshmi ◽  
S. N. Giri
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Interferon Gamma ◽  
Lung Fibrosis ◽  
Molecular Mechanisms ◽  
Antifibrotic Effect

scholarly journals Epitranscriptome of the ventral tegmental area in a deep brain-stimulated chronic unpredictable mild stress mouse model

2020 ◽  
Vol 11 (1) ◽  
pp. 402-418
Author(s):  
Nan Song ◽  
Jun Du ◽  
Yan Gao ◽  
Shenglian Yang
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Ventral Tegmental Area ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Mitogen Activated Protein Kinase ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Ventral Tegmental ◽  
Deep Brain

AbstractDeep brain stimulation (DBS) applied to the nucleus accumbens (NAc) alleviates the depressive symptoms of major depressive disorders. We investigated the mechanism of this effect by assessing gene expression and RNA methylation changes in the ventral tegmental area (VTA) following NAc-DBS in a chronic unpredictable mild stress (CUMS) mouse model of depression. Gene expression and N6-methyladenosine (m6A) levels in the VTA were measured in mice subjected to CUMS and then DBS, and transcriptome-wide m6A changes were profiled using immunoprecipitated methylated RNAs with microarrays, prior to gene ontology analysis. The expression levels of genes linked to neurotransmitter receptors, transporters, transcription factors, neuronal activities, synaptic functions, and mitogen-activated protein kinase and dopamine signaling were upregulated in the VTA upon NAc-DBS. Furthermore, m6A modifications included both hypermethylation and hypomethylation, and changes were positively correlated with the upregulation of some genes. Moreover, the effects of CUMS on gene expression and m6A-mRNA modification were reversed by DBS for some genes. Interestingly, while the expression of certain genes was not changed by DBS, long-term stimulation did alter their m6A modifications. NAc-DBS-induced modifications are correlated largely with upregulation but sometimes downregulation of genes in CUMS mice. Our findings improve the current understanding of the molecular mechanisms underlying DBS effects on depression.

scholarly journals Fecal Microbiota Transplantation Drives Colonic Expression of Immune Activation Genes in a Mouse Model of Antibiotic Use

2021 ◽  
Author(s):  
G. Brett Moreau ◽  
Hale Ozbek ◽  
Pankaj Kumar ◽  
Alyse Frisbee ◽  
Jhansi Leslie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Community Structure ◽  
Mouse Model ◽  
Immune Activation ◽  
Molecular Mechanisms ◽  
Fecal Microbiota Transplantation ◽  
Antibiotic Use ◽  
Fecal Microbiota ◽  
Mucosal Immune Response ◽  
Partial Restoration

Clostridioides difficile infection (CDI) is the leading hospital acquired infection in North America. While the standard treatment for CDI remains antibiotics, fecal microbiota transplantation (FMT) has gained attention as an effective therapy to prevent relapse. Previous work has focused on colonization resistance mounted against C. difficile by FMT-delivered commensals, but the effects of FMT on the gut mucosal immune response are poorly understood. Better understanding of the molecular mechanisms driven by FMT would allow for more targeted therapy against CDI. To address this important gap in knowledge, microbial community structure and host gene expression were assessed after FMT in a mouse model of antibiotic use. Administration of FMT led to a significant increase in microbial diversity and partial restoration of community structure within 48 hours of treatment. RNA sequencing of cecal tissue identified large changes in gene expression between FMT recipient and vehicle control groups. Strikingly, genes upregulated after FMT treatment were enriched in immune activation pathways, many of which were associated with pro-inflammatory immune responses. FMT also upregulated several genes associated with type 2 immunity while repressing several associated with type 3 immunity, trends that are associated with improved response to CDI. These results highlight the interplay between the intestinal microbiota and host transcriptome and identify pathways of interest for exploring the role of FMT on treatment of recurring CDI.

scholarly journals Progesterone Aggravates Lung Fibrosis in a Mouse Model of Systemic Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Fatemeh Vafashoar ◽  
Kazem Mousavizadeh ◽  
Hadi Poormoghim ◽  
Amir Haghighi ◽  
Salar Pashangzadeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Serum Level ◽  
Mouse Model ◽  
Autoimmune Diseases ◽  
Lung Fibrosis ◽  
Normal Lung ◽  
Related Factors ◽  
Progesterone Treatment ◽  
Injured Lung

BackgroundGender-related factors have explained the higher prevalence of autoimmune diseases in women. Sex hormones play a key role in the immune system and parenchymal cells function; therefore, these hormones can be important in the pathogenesis of autoimmune diseases as a risk or beneficial factor. Lung fibrosis is the main cause of mortality in systemic sclerosis, a female predominant autoimmune disease. The objective of this study was to examine the effect of progesterone on lung fibrosis in a mouse model of systemic sclerosis.MethodsMice with bleomycin-induced lung fibrosis treated with progesterone subcutaneously for 21 and 28 days. Blood was collected for hormone and cytokine measurement at the end of treatment then, skin and lung tissues were harvested for histological assessment, gene expression, cytokine, hydroxyproline, and gelatinase measurement.ResultsTrichrome staining and hydroxyproline measurements showed that progesterone treatment increased the content of collagen in fibrotic and normal lung tissues. Progesterone increased α-SMA (P < 0.01), TGF- β (P < 0.05) and decreased MMP9 (P < 0.05) in fibrotic lung tissues. Also progesterone treatment decreased the gene expression of Col1a2 (P <0.05), Ctgf (P <01), End1 (0.001) in bleomycin- injured lung tissues. The serum level of TNF-α was decreased, but the serum level of cortisol was increased by progesterone treatment in fibrotic mice (P< 0.05).ConclusionOur results showed that progesterone aggravates lung fibrosis in a mouse model of systemic sclerosis.

scholarly journals Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xingjie Gao ◽  
Chunyan Zhao ◽  
Nan Zhang ◽  
Xiaoteng Cui ◽  
Yuanyuan Ren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Random Forest ◽  
Mouse Model ◽  
Decision Tree ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
High Expression ◽  
Clinical Prognosis ◽  
Analytical Approaches

Abstract Background The clinical pathologic stages (stage I, II, III-IV) of hepatocellular carcinoma (HCC) are closely linked to the clinical prognosis of patients. This study aims at investigating the gene expression and mutational profile in different clinical pathologic stages of HCC. Methods Based on the TCGA-LIHC cohort, we utilized a series of analytical approaches, such as statistical analysis, random forest, decision tree, principal component analysis (PCA), to identify the differential gene expression and mutational profiles. The expression patterns of several targeting genes were also verified by analyzing the Chinese HLivH060PG02 HCC cohort, several GEO datasets, HPA database, and diethylnitrosamine-induced HCC mouse model. Results We identified a series of targeting genes with copy number variation, which is statistically associated with gene expression. Non-synonymous mutations mainly existed in some genes (e.g.,TTN, TP53, CTNNB1). Nevertheless, no association between gene mutation frequency and pathologic stage distribution was detected. The random forest and decision tree modeling analysis data showed a group of genes related to different HCC pathologic stages, including GAS2L3 and SEMA3F. Additionally, our PCA data indicated several genes associated with different pathologic stages, including SNRPA and SNRPD2. Compared with adjacent normal tissues, we observed a highly expressed level of GAS2L3, SNRPA, and SNRPD2 (P = 0.002) genes in HCC tissues of our HLivH060PG02 cohort. We also detected the high expression pattern of GAS2L3, SEMA3F, SNRPA, and SNRPD2 in the datasets of GSE102079, GSE76427, GSE64041, GSE121248, GSE84005, and the qPCR assay using diethylnitrosamine-induced HCC mouse model. Moreover, SEMA3F and SNRPD2 protein were highly stained in the HCC tissues of the HPA database. The high expression level of these four genes was associated with the poor survival prognosis of HCC cases. Conclusions Our study provides evidence regarding the gene expression and mutational profile in different clinical pathologic stages of TCGA HCC cases. Identifying four targeting genes, including GAS2L3, SNRPA, SNRPD2, and SEMA3F, offers insight into the molecular mechanisms associated with different prognoses of HCC.

scholarly journals Gene expression profiles reveal molecular mechanisms involved in the progression and resolution of bleomycin-induced lung fibrosis

2013 ◽  
Vol 304 (9) ◽  
pp. L593-L601 ◽  
Author(s):  
Sandra Cabrera ◽  
Moises Selman ◽  
Alfredo Lonzano-Bolaños ◽  
Kazuhisa Konishi ◽  
Thomas J. Richards ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Fibrosis ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Transcriptional Profiling ◽  
Gene Expression Profiles ◽  
Regulation Of Transcription ◽  
Fibrotic Response ◽  
Self Organizing Maps ◽  
Transcriptional Signature

Lung fibrosis is the final result of a large number of disorders and is usually considered an irreversible process. However, some evidence suggests that fibrosis could eventually be reversible. In this study we aimed to document the time-related reversibility of bleomycin-induced lung fibrosis and to examine the gene expression profile associated with its initial progression and subsequent resolution. C57BL/6 mice were instilled with a single dose of bleomycin and euthanized at 1, 4, 8, 12, and 16 wk. Control animals received an equal volume of saline. Lung fibrosis was examined by morphology and hydroxyproline content and the transcriptional signature by gene microarray analysis. Our results showed that bleomycin-injured mice developed prominent inflammation at 1 wk, followed by fibrosis that peaked at 2 mo. Then fibrosis resolved until lungs displayed almost normal architecture at 4 mo. Genomewide transcriptional profiling revealed 533 significantly changed genes. Self-organizing maps analysis of these genes identified four clusters based on the temporal pattern of gene expression. Clusters 1 and 2 contained genes upregulated during the inflammatory and fibrotic response and were enriched for extracellular matrix-related genes including several collagens, matrix metalloproteinases, and TIMP-1. Cluster 3 identified upregulated genes during the fibrotic response, and cluster 4 contained genes decreased during inflammation and fibrosis that increased during resolution. Most enriched pathways included genes involved in cell cycle and in regulation of transcription. Our findings corroborate the reversibility of bleomycin-induced lung fibrosis and reveal transcriptional signatures that characterize the progression and resolution.

scholarly journals Loss of ASH1L in developing brains causes autistic-like behaviors in a mouse model

2020 ◽  
Author(s):  
Yuen Gao ◽  
Natalia Duque-Wilckens ◽  
Mohammad B Aljazi ◽  
Yan Wu ◽  
Adam J Moeser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Gene Mutations ◽  
Causal Link ◽  
Autism Spectrum ◽  
Normal Brain ◽  
Critical Function ◽  
Developmental Defects ◽  
Neurodevelopmental Disease

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causal link between ASH1L mutations and ASD/ID remains undetermined. Here we show loss of ASH1L in developing mouse brains is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes a new ASD/ID mouse model revealing the critical function of ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.

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