Evidence mapPaperPMID 41316884Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

SETDB2 Mitigates Podocyte Dysfunction in Diabetic Kidney Disease Through Epigenetic Silencing of SMAD3.

Lanfang Li, Shimin Jiang, Qi Jin, Peng Qu, Yingjie Guo, Xushan Lan, Xinyu Li, Cuiting Sun, Sinan Ai, Xin Li and 5 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
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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

15 authors.

Lanfang LiBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.
Shimin JiangDepartment of Nephrology, China-Japan Friendship Hospital, Beijing, 100029, China.
Qi JinGuang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
Peng QuBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.
Yingjie GuoBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.
Xushan LanBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.
Xinyu LiBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.
Cuiting SunChina-Japan Friendship Hospital, Capital Medical University, Beijing, 100000, China.
Sinan AiDiabetes Department of integrated Chinese and Western medicine, China-Japan Friendship Hospital, Beijing, 100029, China.
Xin LiBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.
Weiliang SunBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.
Jing GuoBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.
Wenge LiDepartment of Nephrology, China-Japan Friendship Hospital, Beijing, 100029, China.
Liang PengBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.ORCID https://orcid.org/0000-0001-8377-0833
Lihong LiuBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.

Funding

Elite Medical Professionals Project of China-Japan Friendship Hospital ZRJY2024-BJ03National Natural Science Foundation of China 82170817:82470845:81970713:82404897Natural Science Foundation of Beijing Municipality 7222160:7254525
6 · The paper itself

Abstract

Podocyte dysfunction represents both an early pathological hallmark and a key driver of proteinuria in diabetic kidney disease (DKD); nevertheless, the potential epigenetic regulatory mechanisms remain poorly defined. Here, the histone methyltransferase SETDB2 is identified as a pivotal epigenetic suppressor of podocyte dysfunction and DKD progression. Glomerular SETDB2 expression exhibits a significant reduce in both DKD patients and mouse models, showing an inverse correlation with disease severity. Podocyte-specific SETDB2 deficiency exacerbates podocytes dysfunction and accelerates DKD progression, whereas its overexpression exerts renal protective effects. Mechanistically, SETDB2 directly enhances H3K9 trimethylation at the Smad3 promoter, thereby repressing SMAD3 expression and activation, ultimately preserving podocyte function. Notably, it identifies TCF21, a transcription factor downregulated in DKD, as a direct upstream regulator of Setdb2 expression via binding to promoter and activating its transcription. Collectively, these findings establish SETDB2 as a critical regulator of podocyte integrity and a promising therapeutic target for DKD.

Indexed as

Diabetic NephropathiesHistone-Lysine N-MethyltransferasePodocytesSmad3 ProteinAnimalsDisease Models, AnimalEpigenesis, GeneticHumansMaleMiceMice, Inbred C57BLHistone-Lysine N-MethyltransferaseSmad3 ProteinSMAD3 protein, humanSmad3 protein, mouseDiabetic kidney diseaseepigenetic regulationhistone methylationpodocyte dysfunctionSETDB2, SMAD3

Identifiers

PMID41316884
PMCPMC12904062

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.