PXD015297

PXD015297 is an original dataset announced via ProteomeXchange.

Title	FERM domain protein 3 Kidney Biopsy
Description	We examined the transcriptional profile of human kidney biopsies, aiming to provide insight into the mechanisms of progressive CKD. This approach led to the identification of FERM domain protein 3, (FRMD3) as a molecular driver of disease. Transcriptome profiling was performed in human renal biopsy tissue and correlated with parameters of kidney function, including estimated glomerular filtration rate (eGFR), degree of renal tubulointerstitial fibrosis (%TIF), as well as CKD progression over a median follow-up period of 60 months. Transcriptome analysis performed in two independent cohorts of patients with CKD (n=24 and n=17, respectively) identified a cluster of genes (n=93) significantly correlated (FDR P<0.05) with eGFR and %TIF, and associated with CKD progression, with enrichment for pathways associated with inflammation and immune-cell mediated infiltration. Expression of FRMD3, a previously reported candidate gene from human genetics studies in CKD, was negatively correlated with indices of CKD severity and progression. Knockdown of FRMD3 in human kidney epithelial cells enhanced fibrotic responses to the cytokine transforming growth factor-beta (TGF-β1). Analysis of FRMD3 binding partners indicated enrichment of proteins implicated in mitochondrial function and remodeling of epithelial adherens junctions. Lentivirus-mediated knockdown of FRMD3 in renal tubule epithelial cells yielded a significant reduction (>35%) in NAD(P)H-dependent oxidoreductase activity, and a corresponding increase in caspase activity (50%). Using global transcriptome profiling we define a cluster of transcripts associated with severity of CKD and identify loss of FRMD3 expression as a potential molecular driver. Loss of FRMD3 expression may contribute to mitochondrial function and TIF.
HostingRepository	PRIDE
AnnounceDate	2024-11-06
AnnouncementXML	Submission_2024-11-06_06:34:01.455.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Matallanas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methionine oxidation with neutral loss of 80 Da; phosphorylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-03 07:13:08	ID requested
⏵ 1	2024-11-06 06:34:02	announced

Kennedy C, Doyle R, Gough O, Mcevoy C, Anallen SM, Hughes M, Sheng X, Crifo B, Andrews D, Gaffney A, Rodriguez J, Kennedy S, Dillon E, Crean D, Zhang W, Yi Z, Nair V, Susztak K, Hirschhorn J, Florez J, Groop PH, Sandholm N, Kretzler M, Mckay GJ, Mcknight AJ, Maxwell AP, Matallanas D, Dorman A, Martin F, Conlon PJ, Sadlier DM, Brennan E, Godson C, A Novel Role for FERM Domain-Containing Protein 3 in CKD. Kidney360, 5(12):1799-1812(2024) [pubmed]

10.34067/kid.0000000602;

submitter keyword: Kidney Human FERM domain protein 3

Eoin Brennan
contact affiliation	Conway Institute Research Fellow Special Lecturer in Clinical Pharmacology School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
contact email	eoin.brennan@ucd.ie
lab head
David Matallanas
contact affiliation	Systems Biology Ireland, University College Dublin
contact email	david.gomez@ucd.ie
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/2024/11/PXD015297

PRIDE project URI

• PRIDE
  1. PXD015297
     1. Label: PRIDE project
     2. Name: FERM domain protein 3 Kidney Biopsy