PXD024035-1

PXD024035 is an original dataset announced via ProteomeXchange.

Title	Orphan nuclear receptor COUP-TFII enhances myofibroblasts glycolysis leading to kidney fibrosis
Description	Recent studies demonstrated that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP-TFII (also known as NR2F2) is an important regulator of glucose and lipid metabolism. Its contribution to organ fibrosis is undefined. Here, we found increased COUP-TFII expression in myofibroblasts in human fibrotic kidneys, lungs, kidney organoids, and mouse kidneys after injury. Genetic ablation of COUP-TFII in mice resulted in attenuation of injury-induced kidney fibrosis. A non-biased proteomic study revealed the suppression of fatty acid oxidation and the enhancement of glycolysis pathways in COUP-TFII overexpressing fibroblasts. Overexpression of COUP-TFII in fibroblasts induced augmented glycolysis and production of alpha smooth muscle actin (αSMA) and collagen1. Knockout of COUP-TFII decreased glycolysis and collagen1 levels in fibroblasts. Chip-qPCR revealed the binding of COUP-TFII on the promoter of PGC1α. Overexpression of COUP-TFII reduced the cellular level of PGC1α. Targeting COUP-TFII serves as a novel treatment approach for mitigating fibrosis in chronic kidney disease and potentially fibrosis in other organs.
HostingRepository	PRIDE
AnnounceDate	2021-04-27
AnnouncementXML	Submission_2021-04-26_22:13:23.549.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marian Kalocsay
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-07 23:59:29	ID requested
⏵ 1	2021-04-26 22:13:23	announced

Dataset with its publication pending

submitter keyword: Kidney, Fibrosis, COUP-TFII, myofibroblasts

Li Li
contact affiliation	Renal Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
contact email	lli29@bwh.harvard.edu
lab head
Marian Kalocsay
contact affiliation	Harvard Medical School
contact email	marian_kalocsay@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024035
     1. Label: PRIDE project
     2. Name: Orphan nuclear receptor COUP-TFII enhances myofibroblasts glycolysis leading to kidney fibrosis