PXD052244

PXD052244 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomic analysis of the role of knocking down NRP1 after OGD/R in primary renal tubular epithelial cells
Description	Neuropilin-1 (NRP1), a co-receptor for various cytokines, including TGF-β, has been identified as a potential therapeutic target for fibrosis. However, its role and mechanism in renal fibrosis remains elusive. Here, we show that NRP1 is upregulated in distal tubular (DT) cells of patients with transplant renal insufficiency and mice with renal ischemia-reperfusion (I-R) injury. Knockout of Nrp1 reduced multiple endpoints of renal injury and fibrosis. We found that Nrp1 facilitates the binding of TNF-α to its receptor in DT cells after renal injury. This signaling results in a downregulation of lysine crotonylation of the metabolic enzyme Cox4i1, decreased cellular energetics and exacerbation of renal injury. Furthermore, by single-cell RNA-sequencing we found that Nrp1-positive DT cells secrete collagen and communicate with myofibroblasts, exacerbating acute kidney injury (AKI)-induced renal fibrosis by activating Smad3. Dual genetic deletion of Nrp1 and Tgfbr1 in DT cells better improves renal injury and fibrosis than either single knockout. Together, these results reveal that targeting of NRP1 represents a promising strategy for the treatment of AKI and subsequent chronic kidney disease
HostingRepository	PRIDE
AnnounceDate	2024-06-03
AnnouncementXML	Submission_2024-06-03_03:53:25.916.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yinzheng Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-13 21:26:17	ID requested
⏵ 1	2024-06-03 03:53:26	announced

Dataset with its publication pending

submitter keyword: lysine crotonylation,NRP1, chronic kidney disease, acute kidney injury, aerobic metabolism

Rui Zeng
contact affiliation	Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
contact email	lyzhengmz@163.com
lab head
Yinzheng Li
contact affiliation	Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
contact email	lyzhengmz@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052244
     1. Label: PRIDE project
     2. Name: Quantitative proteomic analysis of the role of knocking down NRP1 after OGD/R in primary renal tubular epithelial cells