Proteomics

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Proteomic experiment of lysine crotonylation modification to analysis of the role of knocking down NRP1 after IR in kidney


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney

SUBMITTER: Yinzheng Li  

LAB HEAD: Rui Zeng

PROVIDER: PXD052293 | Pride | 2024-06-03

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
RE560LPCr_Sham_Slot2-50_1_2949.d.zip Other
RE560LPCr_Tmx_Slot2-52_1_2953.d.zip Other
RE560LPCr_Vehi_Slot2-51_1_2951.d.zip Other
RE560LPCr_combined.zip Other
RE560LQ_Sham_Slot1-4_1_11.d.zip Other
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