PXD064267-1

PXD064267 is an original dataset announced via ProteomeXchange.

Title	Extracellular Matrix Stiffness determines kidney metabolism reprogramming after AKI
Description	Kidney repair after acute kidney injury (AKI) relies on a well-regulated extracellular matrix (ECM) that provides structural and mechanical cues. Fibroblasts and pericytes, key ECM producers, are rapidly activated post-injury, but ECM-driven repair mechanisms remain unclear. Using proteomics, spatial transcriptomics, and animal models, we profiled the landscape of matrix proteins altered post-AKI, highlighting microfibrillar-associated protein 2 (Mfap2) as a critical ECM component. Predominantly derived from fibroblasts and pericytes, Mfap2 loss impairs kidney architecture and metabolism, worsening AKI. Proteomics revealed that Mfap2 knockout suppresses tubule-derived Hmgcs2 via Esr2-mediated transcriptional repression and enhanced succinylation. Phosphoproteomics showed Mfap2 deletion hyperactivates MAPK and Lats1 in tubules, independent of integrin signaling and Yap/Taz. Mechanistically, reduced Lats1 boosts Esr2 transcription without affecting its degradation. Esr2 agonists restored kidney function in Mfap2-deficient models. Thus, Mfap2 governs ECM stiffness, transduces mechanical signals, reprograms metabolism, and fosters a pro-repair microenvironment critical for AKI recovery.
HostingRepository	PRIDE
AnnounceDate	2025-12-24
AnnouncementXML	Submission_2025-12-23_16:33:05.353.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenxue Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-24 14:31:25	ID requested
⏵ 1	2025-12-23 16:33:05	announced

Dataset with its publication pending

submitter keyword: Acute kidney injury

Extracellular Matrix

Mfap2, Proteomics

Phosphoproteomics

Yansheng Liu
contact affiliation	Yale School of Medicine
contact email	yansheng.liu@yale.edu
lab head
Wenxue Li
contact affiliation	Yale University
contact email	wenxue.li@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064267
     1. Label: PRIDE project
     2. Name: Extracellular Matrix Stiffness determines kidney metabolism reprogramming after AKI