Evidence map›Paper›PMID 41776110›Full record

ArticleNature metabolism2026

Early-activated extracellular matrix proteins shape the metabolic and spatial dynamics of the kidney fibrotic microenvironment.

Yuan Gui, Wenxue Li, Jia-Jun Liu, Yuanyuan Wang, Cameron Jones, Riddhi Bansal, Samantha Mae Mallari, Henry Wells Shaffer, Yanbao Yu, Haiyan Fu and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature metabolism, 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

14 authors.

Yuan GuiDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
Wenxue LiYale Cancer Biology Institute, Yale University, West Haven, CT, USA.ORCID http://orcid.org/0000-0002-8902-0184
Jia-Jun LiuOrgan Pathobiology and Therapeutics Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Yuanyuan WangDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.ORCID http://orcid.org/0000-0002-6693-643X
Cameron JonesDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
Riddhi BansalDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
Samantha Mae MallariDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
Henry Wells ShafferDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
Yanbao YuDepartment of Chemistry and Biochemistry, University of Delaware, Newark, DE, USA.ORCID http://orcid.org/0000-0003-2994-1974
Haiyan FuDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Tracy T TangVivace Therapeutics, Inc., San Mateo, CA, USA.
Silvia LiuOrgan Pathobiology and Therapeutics Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Yansheng LiuYale Cancer Biology Institute, Yale University, West Haven, CT, USA.ORCID http://orcid.org/0000-0002-2626-3912
Dong ZhouDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA. dzhou@uchc.edu.ORCID http://orcid.org/0000-0003-1981-8745

Funding

Pittsburgh Liver Research CenterP30DK120531 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVID A GELLER · 2019 to 2026
$10.9M
Importance of cell-matrix interactions in kidney repair after acute kidney injuryR01DK132059 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI Dong Zhou · 2023 to 2026
$1.9M
High-Throughput Computing for Genomics and Bioinformatics ResearchS10OD028483 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, ADRIAN V · 2021 to 2021
$574k
Early and Transient Activation of Fibroblasts Promotes Tubule Repair after Acute Kidney InjuryK01DK116816 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZHOU, DONG · 2019 to 2021
$509k
The formation of kidney local microenvironment after acute kidney injury.R03DK128529 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ZHOU, DONG · 2021 to 2022
$246k
American Heart Association (American Heart Association, Inc.) 25CDA1435759NIDDK NIH HHS K01 DK116816NIDDK NIH HHS P30 DK120531NIDDK NIH HHS R01 DK132059NIDDK NIH HHS R03 DK128529U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM159862U.S. Department of Health & Human Services | National Institutes of Health (NIH) S10OD028483U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK116816U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK128529U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK132059
6 · The paper itself

Abstract

The fibrotic kidney microenvironment is shaped by cellular crosstalk, extracellular matrix (ECM) remodelling, metabolic reprogramming and spatial heterogeneity. While late-stage ECM changes dominate fibrosis, the role of early-activated matrix proteins remains unclear. Here we show that ECM1 is an early regulator of kidney remodelling. Global Ecm1 knockout mice develop spontaneous fibrosis and early death, whereas ECM1 levels markedly increase in biofluids during chronic kidney disease. Targeting Ecm1 through AAV9-mediated knockdown or fibroblast-specific deletion substantially reduces renal fibrosis. Mechanistically, Ecm1 deletion disrupts the integrin α2β1-RhoC axis, suppressing YAP activity. Reduced YAP nuclear translocation and diminished YAP-TEAD4 complex formation relieve TEAD4-mediated repression of Pgc1a, enhancing mitochondrial oxidative phosphorylation (OXPHOS) and promoting repair. Spatial transcriptomics and proteomics confirm this mechano-metabolic pathway, revealing mitochondrial reprogramming in tubules that counteracts fibrotic progression. Notably, YAP inactivation in fibroblasts limits aberrant activation without impairing their OXPHOS. This selective ECM-mitochondrial crosstalk uncovers a mechano-metabolic pathway in which mitochondrial shifts drive defence against kidney fibrosis.

Indexed as

Cellular MicroenvironmentExtracellular Matrix ProteinsKidneyKidney DiseasesAnimalsExtracellular MatrixFibrosisMetabolic ReprogrammingMiceMice, KnockoutMitochondriaOxidative PhosphorylationExtracellular Matrix Proteins

Identifiers

PMID41776110

What Socratic holds

Textmetadata
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.