Dataset Information

FERM domain protein 3 Kidney Biopsy

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Chronic Kidney Disease

SUBMITTER: David Matallanas

LAB HEAD: Eoin Brennan

PROVIDER: PXD015297 | Pride | 2024-11-06

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	160816_OG_HK2_IP_EV_IgG_N1a.raw	Raw
	160816_OG_HK2_IP_EV_IgG_N1b.raw	Raw
	160816_OG_HK2_IP_EV_IgG_N2a.raw	Raw
	160816_OG_HK2_IP_EV_IgG_N2b.raw	Raw
	160816_OG_HK2_IP_EV_IgG_N3a.raw	Raw

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Publications

A Novel Role for FERM Domain-Containing Protein 3 (FRMD3) in CKD.

Kennedy Ciarán C Doyle Ross R Gough Oisin O Mcevoy Caitriona C Anallen Susan Mc SM Hughes Maria M Sheng Xin X Crifo Bianca B Andrews Darrell D Gaffney Andrew A Rodriguez Javier J Kennedy Susan S Dillon Eugene E Crean Daniel D Zhang Weijia W Yi Zhengzi Z Nair Viji V Susztak Katalin K Hirschhorn Joel J Florez Jose J Groop Per-Henrik PH Sandholm Niina N Kretzler Matthias M Mckay Gareth J GJ Mcknight Amy Jayne AJ Maxwell Alexander P AP Matallanas David D Dorman Anthony A Martin Finian F Conlon Peter J PJ Sadlier Denise M DM Brennan Eoin E Godson Catherine C

Kidney360 20241016

<h4>Background</h4>Currently there are limited methods to link disease severity and risk of disease progression in Chronic Kidney Disease (CKD). To better understand this potential relationship, we interrogated the renal transcriptomic profile of individuals with CKD with measures of CKD severity and identified FERM-domain containing protein 3 (FRMD3) as a candidate gene for follow-up study.<h4>Methods</h4>RNA-seq was used to profile the transcriptome of CKD biopsies from the North Dublin Renal ...[more]

PMID: 39450948

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