PXD006573

PXD006573 is an original dataset announced via ProteomeXchange.

Title	Mouse Liver LC-MS/MS LNA miR-676 treated dbdb mice
Description	Over 40 % of microRNAs are located in introns of coding genes, and many intronic microRNAs are co-regulated with their host genes. In such cases of co-regulation, the products of host genes and their intronic microRNAs can cooperate to coordinately regulate biologically important pathways. Therefore, we screened intronic microRNAs dysregulated in liver of obese mouse models to identify previously uncharacterized coding host genes that may contribute to the pathogenesis of obesity-associated insulin resistance and type 2 diabetes mellitus. Our approach identified that expression of both Ectodysplasin A (Eda), the causal gene of X-linked hypohidrotic ectodermal dysplasia (XLHED; MIM 305100) and its intronic microRNA, miR-676, was strongly increased in liver of obese mouse models. Moreover, hepatic EDA expression is increased in obese human subjects, reduced upon weight loss, and its hepatic expression correlates with systemic insulin resistance. Eda expression in murine liver is controlled via PPARg activation, increases in circulation and promotes JNK activation and inhibitory serine phosphorylation of IRS1 in skeletal muscle. Consistently, bi-directional modulation of hepatic Eda expression in mouse models affects systemic glucose metabolism with alterations of muscle insulin signaling, revealing a novel role of EDA as an obesity-associated hepatokine, which impairs insulin sensitivity in skeletal muscle.
HostingRepository	PRIDE
AnnounceDate	2019-03-06
AnnouncementXML	Submission_2019-03-06_02:11:16.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hendrik Nolte
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-23 05:31:12	ID requested
1	2017-11-14 06:40:14	announced
2	2017-11-16 07:05:56	announced	Updated project metadata.
⏵ 3	2019-03-06 02:11:18	announced	Updated project metadata.

Awazawa M, Gabel P, Tsaousidou E, Nolte H, Kr, ü, ger M, Schmitz J, Ackermann PJ, Brandt C, Altm, ü, ller J, Motameny S, Wunderlich FT, Kornfeld JW, Bl, ü, her M, Br, ü, ning JC, A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle. Nat Med, 23(12):1466-1473(2017) [pubmed]

curator keyword: Biological

submitter keyword: Mouse, Liver, LC-MSMS, miR-676,dbdb mice

Marcus Krüger
contact affiliation	Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 26, Cologne, Germany
contact email	marcus.krueger@uni-koeln.de
lab head
Hendrik Nolte
contact affiliation	Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)
contact email	h.nolte@uni-koeln.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/11/PXD006573

PRIDE project URI

• PRIDE
  1. PXD006573
     1. Label: PRIDE project
     2. Name: Mouse Liver LC-MS/MS LNA miR-676 treated dbdb mice