PXD047057

PXD047057 is an original dataset announced via ProteomeXchange.

Title	Repairing of isoaspartyl residues by PCMT1 alleviates renal fibrosis through the repression of TGF-β1/TGFBR2/Smad signaling pathway
Description	Protein L-isoaspartyl/D-aspartyl Methyltransferase (PCMT1) plays a pivotal role in repairing a spontaneous post-translational modification (PTM) of L-isoaspartyl residues resulted from asparagine deamidation or aspartate isomerization. This PTM is particularly important for extracellular matrix (ECM) proteins because their low turnover rate and are susceptible to factors that could accelerate such modification. Therefore, it becomes imperative to comprehensively investigate the impact of PCMT1 on ECM homeostasis and its associated pathological alterations. In this study, we revealed that secreted PCMT1 repairs the isoaspartyl residues of the TGFBR2 protein on the cell membrane to suppress TGF-β1/Smad pathway. Through this novel PTM regulation, PCMT1 played essential roles in combating renal fibrosis, as lack of PCMT1 worsened tubular injury, collagen deposition, myofibroblast activation, and macrophage infiltration in total kidney and tubular contexts in a mouse model of chronic kidney disease. Moreover, PCMT1 level decreased in fibrotic kidney tissues and inversely related to kidney function in mice and in humans. Our study highlights the important function of PCMT1 in modifying proteins in the extracellular space and identified a novel role of PCMT1 in regulating TGF-β1 pathway in renal fibrosis. This study holds the potential of innovative therapeutic avenue for the mitigation of renal fibrosis.
HostingRepository	PRIDE
AnnounceDate	2025-03-18
AnnouncementXML	Submission_2025-03-18_00:14:59.282.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yutong Hou
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-18 07:32:11	ID requested
⏵ 1	2025-03-18 00:15:00	announced

Xia J, Hou Y, Wang J, Zhang J, Wu J, Yu X, Cai H, Yang W, Xu Y, Mou S, Repair of Isoaspartyl Residues by PCMT1 and Kidney Fibrosis. J Am Soc Nephrol, ():(2025) [pubmed]

10.1681/asn.0000000652;

submitter keyword: PCMT1, TGF-β1-Smad pathway, isoaspartyl residues, TGFBR2, extracellular matrix, renal fibrosis

Jia Xia
contact affiliation	Department of Nephrology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, P.R. China.
contact email	15900470566@163.com
lab head
Yutong Hou
contact affiliation	SJTU
contact email	houyt9@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047057
     1. Label: PRIDE project
     2. Name: Repairing of isoaspartyl residues by PCMT1 alleviates renal fibrosis through the repression of TGF-β1/TGFBR2/Smad signaling pathway