Evidence mapPaperPMID 42272503Full record

ArticleFundamental research2026

Spatial atlas of human diabetic kidney uncovered podocyte-driven metabolic-inflammatory crosstalk via glycerolipid reprogramming and DUSP4/MMP3 axis.

Shi Qiu, Zhibo Wang, Sifan Guo, Dandan Xie, Ying Cai, Xian Wang, Qiang Yang, Qiqi Zhao, Yu Guan, Chunsheng Lin and 5 more

Abstract read
In one paragraph

Article in Fundamental research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Shi QiuSchool of Chinese Medicine, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Haikou 571199, China.
Zhibo WangSchool of Chinese Medicine, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Haikou 571199, China.
Sifan GuoSchool of Chinese Medicine, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Haikou 571199, China.
Dandan XieSchool of Chinese Medicine, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Haikou 571199, China.
Ying CaiSchool of Chinese Medicine, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Haikou 571199, China.
Xian WangSchool of Chinese Medicine, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Haikou 571199, China.
Qiang YangCollege of Basic Medicine, Graduate School, Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Qiqi ZhaoCollege of Basic Medicine, Graduate School, Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Yu GuanCollege of Basic Medicine, Graduate School, Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Chunsheng LinCollege of Basic Medicine, Graduate School, Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Hong YaoFirst Affiliated Hospital, Harbin Medical University, Harbin 150040, China.
Songqi TangSchool of Chinese Medicine, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Haikou 571199, China.
Wenjie SunDepartment of Nephrology, Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Yiqiang XieSchool of Chinese Medicine, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Haikou 571199, China.
Aihua ZhangSchool of Chinese Medicine, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Haikou 571199, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diabetic nephropathy (DN) pathogenesis remains elusive due to the lack of comprehensive spatial molecular characterization related to tissue pathological signatures. Here, we construct the spatial single-cell atlas of human DN kidneys using clinical formalin-fixed paraffin-embedded (FFPE) biopsies, integrating spatial transcriptomics, metabolomics, and scRNA-seq across 39,006 cells. We identify podocytes as spatial metabolic-inflammatory hubs orchestrating DN progression, exhibiting conserved dysregulation of glycerolipid metabolism and MAPK signaling in human and diabetic mice kidneys. Spatial multi-omics of inflammatory and glomerular injury zones reveal 179 and 234 differentially expressed genes enriched in MAPK pathways. Crucially, urinary MMP3, traced to glomerular injury zones, emerges as a non-invasive diagnostic biomarker. We further demonstrate that astragaloside IV (ASIV) attenuates DN by dual targeting: rescuing DUSP4-mediated MAPK suppression (reducing p-p38/JNK) and normalizing glycerolipid metabolites (D-glycerate, 3-PGA), thereby downregulating MMP3/IL-6/IL-1β and suppressing oxidative stress in podocytes. This work redefines DN as a disorder of spatially organized metabolic-inflammation synergy, establishing urinary MMP3 for clinical detection and ASIV as a therapeutic agent targeting the DUSP4-MAPK-glycerolipid axis, providing a roadmap for precision interventions in DN.

Indexed as

DUSP4-MAPK pathwayGlycerolipid metabolismMMP3PodocytesSpatial transcriptomics

Identifiers

PMID42272503
PMCPMC13247493

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.