Evidence map›Paper›PMID 42129791›Full record

ArticleCell communication and signaling : CCS2026

PLCε regulates podocyte differentiation and TGF-β1 responses via alteration of SMAD2/SMAD3 ratio.

Carl J May, Sarah E Hunter, Agnieszka Bierzynska, Lan Ni, Katherine R Bull, Aneesha Bhandari, Gavin I Welsh, Moin A Saleem

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In one paragraph

Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Carl J MayBristol Renal, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, England.
Sarah E HunterBristol Renal, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, England.
Agnieszka BierzynskaBristol Renal, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, England.
Lan NiBristol Renal, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, England.
Katherine R BullNuffield Dept of Medicine, Centre for Cellular and Molecular Physiology, Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford, OX3 7XB, England.
Aneesha BhandariNuffield Dept of Medicine, Centre for Cellular and Molecular Physiology, Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford, OX3 7XB, England.
Gavin I WelshBristol Renal, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, England.
Moin A SaleemBristol Renal, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, England. m.saleem@bristol.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAmongst genetic causes of nephrotic syndrome (NS), mutations in the PLCΕ1 gene have been described in patients with early onset NS and diffuse mesangial sclerosis (DMS). However, little is known about how these mutations alter podocyte biology although a role in podocyte differentiation has been proposed (Yu S, et al. Exp Mol Med. 52(4):594-603,2020).

methodsTo explore the role of PLCε in podocytes, A conditionally immortalised human podocyte cell line was generated from a patient with early onset NS, due to a nonsense PLCΕ1 mutation, resulting histologically in diffuse mesangial sclerosis (DMS).

resultsIn comparison to wild type podocytes, the PLCΕ1 mutant podocyte cell has reduced epithelial features, altered actin cytoskeleton and significantly lower levels of the epithelial marker ZO-1.

conclusionsWe demonstrate that PLCε deficiency is associated with functionally impaired TGF-β1 responses with an altered SMAD2/SMAD3 ratio and absent SMAD2 phosphorylation, resulting in loss of the motility response to TGF-β1. We further show that PLCE1 knockdown in wild-type podocytes recapitulates this phenotype by knock-down of PLCΕ1 in wild-type podocytes. This work reveals that disease-causing mutations in PLCΕ1 result in podocyte dedifferentiation and uncovers a novel association between PLCΕ1 deficiency and SMAD2/3 signalling signalling in maintaining podocyte differentiation.

Indexed as

Cell DifferentiationPhosphoinositide Phospholipase CPodocytesSmad2 ProteinSmad3 ProteinTransforming Growth Factor beta1Cell LineHumansPhosphorylationSignal TransductionPhosphoinositide Phospholipase Cphospholipase C epsilonSmad2 ProteinSMAD2 protein, humanSmad3 ProteinTransforming Growth Factor beta1Cell communicationGlomerular diseasePLCεPodocyte injuryProteinuriaTGF-β1 signaling

Identifiers

PMID42129791
PMCPMC13340390

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.