Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hormonal Therapies Upregulate MANF and Overcome Female Susceptibility to Immune Checkpoint Inhibitor-Myocarditis

ABSTRACT: Hormonal Therapies Upregulate MANF and Overcome Female Susceptibility to Immune Checkpoint Inhibitor-Myocarditis

PROVIDER: PRJNA880892 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR21594534_1.fastq.gz	Fastqsanger.gz
	SRR21594534_2.fastq.gz	Fastqsanger.gz
	SRR21594535_1.fastq.gz	Fastqsanger.gz
	SRR21594535_2.fastq.gz	Fastqsanger.gz
	SRR21594536_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Hormonal Therapies Upregulate MANF and Overcome Female Susceptibility to Immune Checkpoint Inhibitor-Myocarditis

Project description:Immune checkpoint inhibitors (ICIs) have been increasingly used in combination for cancer treatment, but are particularly associated with myocarditis. Here, we report that tumor-bearing mice exhibited response to treatment with combinatorial anti-PD-1 (programmed cell death 1) and anti-CTLA-4 (Cytotoxic T-lymphocyte Antigen-4) antibodies but also presented with cardiovascular toxicities observed clinically with ICI therapy, including myocarditis and arrhythmia. Female mice were preferentially affected with myocarditis compared to male mice, consistent with a previously described genetic model of ICI-myocarditis as well as emerging clinical data. Mechanistically, myocardial tissue from ICI-treated mice, the genetic mouse model, and human heart tissue from affected patients with ICI-myocarditis all exhibited downregulation of MANF (Mesencephalic Astrocyte Derived Neurotrophic Factor) and HSPA5 (Heat Shock 70kDa Protein 5) in the heart; this downregulation was particularly striking in female mice. ICI-myocarditis was amplified by heart-specific genetic deletion of mouse Manf and was attenuated by administration of recombinant MANF protein, suggesting a causal role. Ironically, both MANF and HSPA5 were transcriptionally induced by liganded estrogen receptor-βbeta and inhibited by androgen receptor. However, ICI treatment reduced serum estradiol concentration to a greater extent in female compared to male mice. Treatment with an estrogen receptor β-specific agonist as well as androgen depletion therapy attenuated ICI-associated cardiac effects. Taken together, our data suggest that ICI treatment inhibits the estradiol-dependent expression of MANF/HSPA5 in the heart, curtailing the cardiomyocyte response to immune injury. This endocrine-cardiac-immune pathway offers new insights into the mechanisms of sex differences in cardiac disease and may offer treatment strategies for ICI-myocarditis.

2022-09-18 | GSE213468 | GEO

Hormonal therapies up-regulate MANF and overcome female susceptibility to immune checkpoint inhibitor myocarditis.

Project description:Immune checkpoint inhibitors (ICIs) have been increasingly used in combination for cancer treatment but are associated with myocarditis. Here, we report that tumor-bearing mice exhibited response to treatment with combinatorial anti-programmed cell death 1 and anti-cytotoxic T lymphocyte antigen-4 antibodies but also presented with cardiovascular toxicities observed clinically with ICI therapy, including myocarditis and arrhythmia. Female mice were preferentially affected with myocarditis compared to male mice, consistent with a previously described genetic model of ICI myocarditis and emerging clinical data. Mechanistically, myocardial tissue from ICI-treated mice, the genetic mouse model, and human heart tissue from affected patients with ICI myocarditis all exhibited down-regulation of MANF (mesencephalic astrocyte-derived neurotrophic factor) and HSPA5 (heat shock 70-kDa protein 5) in the heart; this down-regulation was particularly notable in female mice. ICI myocarditis was amplified by heart-specific genetic deletion of mouse Manf and was attenuated by administration of recombinant MANF protein, suggesting a causal role. Ironically, both MANF and HSPA5 were transcriptionally induced by liganded estrogen receptor β and inhibited by androgen receptor. However, ICI treatment reduced serum estradiol concentration to a greater extent in female compared to male mice. Treatment with an estrogen receptor β-specific agonist and androgen depletion therapy attenuated ICI-associated cardiac effects. Together, our data suggest that ICI treatment inhibits estradiol-dependent expression of MANF/HSPA5 in the heart, curtailing the cardiomyocyte response to immune injury. This endocrine-cardiac-immune pathway offers new insights into the mechanisms of sex differences in cardiac disease and may offer treatment strategies for ICI myocarditis.

| S-EPMC9809130 | biostudies-literature

Expression profile analysis of Drosophila melanogaster embryonic and larval MANF mutants together with paternal rescue and overexpression conditions

Project description:To find out possible pathways and processes influenced by DmMANF we compared the changes in MANF null and overexpressing animals. We used two developmental stages of Drosophila, st 17 embryos and 29-50 hrs after egg laying (AEL) larvae. The timing were decided according to the lethality of MANF mutants with or without maternal contribution of MANF. Maternal and zygotic MANF mutants (MANFmzD96) were compared to paternal rescue and wild type embryos of the same age. Zygotic MANF mutants (MANFD96) with maternal contribution were compared to wild type and MANF ectopic overexpression larvae harvested well before the average lethality occured (75 hrs AEL). The changes in expression profiles were more drastic in MANFmzD96 embryos than in MANFD96 larvae. Gene ontology annotations were analyzed and clustered by DAVID. The major result was alterations in membranes, changes in membrane transporter expressions and disturbed intracellular membrane traffic. The results were verified by qPCR and transmission electron microscopy. Two developmental stages - 21-24 hrs and 29-50 hrs AEL of MANFD96 mutants without and with maternal contribution were compared to wild type (Wmix means crossed w1118 x w- ) and with paternal rescue or ectopic overexpression of MANF respectively by Drosophila Agilent microarray expression platform.

2012-04-19 | E-GEOD-28820 | biostudies-arrayexpress

Gene expression profile of MANF-deficient Cx3cr1+ macrophages during muscle regeneration

Project description:RNA sequencing analysis of MANF-deficient macrophages revealed changes in key cellular processes.

2023-02-13 | GSE224983 | GEO

The neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis in Caenorhabditis elegans

Project description:Mesencephalic astrocyte-derived neurotrophic factor (MANF) is the only neurotrophic factor to be conserved between C. elegans and humans. MANF is a unique neutrotophic factor, as it is a resident ER protein in cells that express it and has a role in regulating ER stress response to tunicamycin exposure and pathogenic Pseudomonas exposure. We sought to further understand the role of MANF by comparing a deletion allele, an overexpression line, and the wild-type in this RNAseq experiment.

2024-10-03 | GSE278675 | GEO

Expression profile analysis of Drosophila melanogaster embryonic and larval MANF mutants together with paternal rescue and overexpression conditions

2012-04-20 | GSE28820 | GEO

Rat (Rattus norvegicus) RNA-Seq containing SHAM, STROKE and MANF groups

Project description:Samples from three groups, SHAM operated group and two STROKE operated groups treated two days post operation with AAV1-eGFP control and AAV1-MANF treatment were sequenced and analysed for differential gene expression

2020-04-12 | E-MTAB-8339 | biostudies-arrayexpress

Dilated cardiomyopathy vs Myocarditis

Project description:Sequencing data of biopsies from Myocarditis and DCM patients

2018-09-28 | GSE120567 | GEO

Differential Gene expression of C. elegans larvae following tunicamycin treatment in the absence of manf-1

Project description:Microarray analysis was performed to evaluate the changes in gene expression that are associated with manf-1 deficiency with and without exposure to tunicamycin. RNA was isolated from four groups, (wildtype (N2) and manf-1 mutant (tm3603) L1 stage larve with and without 5 hours exposure to tunicmycin (5microgram/milliliter)) for transcriptomic profiles analysis

2019-06-26 | GSE118294 | GEO

Gene expression profile in Liver of young and old mice with MANF overexpression

Project description:MANF overexpression in old mice had a beneficial effect in the liver and restored expression levels of several metabolic genes.

2019-03-01 | GSE123115 | GEO

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