Evidence map›Paper›PMID 41005570›Full record

ArticleKidney international2026

Critical role of transcription factor SOX4 in tubular epithelial cell dedifferentiation and fibroblast activation during kidney fibrosis.

Hao Du, Baihai Jiao, Jian Xing, Dong Yang, Melanie Tran, Penghua Wang, Zhaoyong Hu, Véronique Lefebvre, Dong Zhou, Yanlin Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

10 citing papers in PubMed.

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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

10 authors.

Hao DuDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA; Department of Cell Biology, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Baihai JiaoDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Jian XingDepartment of Pathology, Yale University, New Haven, Connecticut, USA.
Dong YangDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Melanie TranDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Penghua WangDepartment of Immunology, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Zhaoyong HuSection of Nephrology, Baylor College of Medicine, Houston, Texas, USA.
Véronique LefebvreDivision of Orthopaedics, Department of Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Dong ZhouDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Yanlin WangDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA; Department of Cell Biology, University of Connecticut School of Medicine, Farmington, Connecticut, USA; Institute for Systems Genomics, University of Connecticut, Farmington, Connecticut, USA; Renal Section, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA. Electronic address: yanlwang@uchc.edu.

Funding

Cellular and Molecular Mechanisms of Renal FibrosisR01DK095835 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI WANG, YANLIN · 2012 to 2021
$3.2M
Roles of SOXC proteins in osteogenic cellsR01AR068308 · NIAMS · CLEVELAND CLINIC LERNER COM-CWRU · PI LEFEBVRE, VERONIQUE M · 2016 to 2020
$2.4M
Novel mechanisms of kidney inflammation and fibrosisR01DK134475 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI YANLIN WANG · 2023 to 2026
$2.1M
BLRD VA I01 BX002650NIAMS NIH HHS R01 AR068308NIDDK NIH HHS R01 DK095835NIDDK NIH HHS R01 DK134475
6 · The paper itself

Abstract

introductionChronic kidney disease (CKD) is a widely prevalent health issue globally. A striking pathological feature of CKD is kidney fibrosis characterized by excessive production and deposition of extracellular matrix (ECM). Tubular epithelial cell (TEC) dedifferentiation and fibroblast activation contribute to the pathogenesis of kidney fibrosis. However, the molecular mechanisms underlying TEC dedifferentiation and fibroblast activation are not fully understood. Here, we investigated the role of SRY-box transcription factor 4 (SOX4) in regulating TEC dedifferentiation and fibroblast activation during the development of CKD.

methodsWe generated global, TEC-specific, and fibroblast-specific SOX4 knockout mice. These mice were subjected to three preclinical models of kidney fibrosis induced by unilateral ureteral obstruction, ischemia-reperfusion injury, or high-dose folic acid to examine the role of SOX4 in TEC dedifferentiation and fibroblast activation during the development of kidney fibrosis. Cultured TECs and fibroblasts were employed to determine the role and molecular mechanisms of SOX4 in regulating TEC dedifferentiation and fibroblast activation in vitro.

resultsSOX4 was induced in the injured kidneys but its deficiency inhibits TEC dedifferentiation, fibroblast activation and further impeded the development of kidney fibrosis in mice. In vitro, knockdown of SOX4 preserved the epithelial phenotype and inhibited fibroblast activation induced by transforming growth factor-β1 (TGF-β1). Mechanistically, SOX4 facilitated the TGF-β1-Smad3 signaling pathway to promote TEC dedifferentiation and fibroblast activation.

conclusionsOur findings identify SOX4 as a critical factor in TEC dedifferentiation and fibroblast activation suggesting SOX4 may serve as a potential therapeutic target for the treatment of CKD.

Indexed as

Cell DedifferentiationEpithelial CellsFibroblastsKidney TubulesRenal Insufficiency, ChronicSOXC Transcription FactorsAnimalsCells, CulturedDisease Models, AnimalFibrosisFolic AcidMaleMiceMice, Inbred C57BLMice, KnockoutReperfusion InjuryFolic AcidSmad3 ProteinSmad3 protein, mouseSox4 protein, mouseSOXC Transcription FactorsTgfb1 protein, mouseTransforming Growth Factor beta1fibroblast activationkidney fibrosisSmad3SOX4TGF-βtubular epithelial cell dedifferentiation

Identifiers

PMID41005570
PMCPMC12548802

What OpenQuestion holds

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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 OpenQuestion graph.