PXD066935

PXD066935 is an original dataset announced via ProteomeXchange.

Title	Testican-2 interaction with the extracellular matrix and podocyte protection
Description	Background: Testican-2 is a podocyte-derived glycoprotein encoded by SPOCK2. Circulating levels of testican-2 are associated with less glomerulosclerosis and better kidney prognosis, but its biological function in the podocyte is unknown. Methods: We studied the protective effect of testican-2 on immortalized cultured human podocytes and in mice treated with adriamycin. We used immunoprecipitation-mass spectrometry to identify binding partners of testican-2 and Bio-Layer Interferometry to characterize these protein-protein interactions. Using global Spock2 knockout mice, we assessed the impact of testican-2 deficiency in models of podocyte injury and also tested whether exogenous testican-2 confers podocyte protection in these testican-2 deficient mice. Finally, we analyzed testican-2 expression in human kidney biopsy samples. Results: Testican-2 reduced reduces adriamycin-induced podocyte injury in cultured human podocytes and mice. Vitronectin is a strong binding partner for testican-2, and testican-2 inhibited inhibits the interaction between vitronectin and integrin αVβ3, an important effector of podocyte injury. Consistent with this, testican-2 administration reduced reduces activation of integrin β3 in injured podocytes. Further, Spock2 deficiency increased increases susceptibility to podocyte injury due to adriamcyin and streptozotocin induced diabetes, as determined by albuminuria, foot process effacement, nephrin expression and WT1-positive podocyte number. Importantly, exogenous testican-2 circulated circulates to the kidney, bound binds to vitronectin, reduced reduces vitronectin-integrin β3 interaction, and reduced reduces podocyte injury in Spock2 deficient mice. Finally, glomerular testican-2 expression was is reduced in human focal segmental glomerulosclerosis and diabetic kidney disease, but not tubulointerstitial nephropathy. Conclusions: These findings identify a potential mechanism for testican-2 mediated kidney protection and highlight an opportunity to therapeutically target the podocyte’s interaction with its extracellular matrix.
HostingRepository	PRIDE
AnnounceDate	2026-01-19
AnnouncementXML	Submission_2026-01-18_16:08:03.030.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD066935
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Donghai Wen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-04 08:09:03	ID requested
⏵ 1	2026-01-18 16:08:04	announced

10.6019/PXD066935;

10.1681/asn.0000000915;

Wen D, Zhang Q, van Agthoven J, Weins A, Rosales IA, Zhou W, Kim T, Vela Parada X, Colvin RB, Pollak MR, Grams ME, Schmidt IM, Waikar SS, Arnaout MA, Rhee EP, Testican-2 Interaction with the Extracellular Matrix and Podocyte Protection. J Am Soc Nephrol, ():(2025) [pubmed]

submitter keyword: testican-2 binding protein, podocyte,human

Donghai Wen
contact affiliation	MGH
contact email	dwen@bwh.harvard.edu
lab head
Donghai Wen
contact affiliation	MGH
contact email	dwen@bwh.harvard.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/01/PXD066935

PRIDE project URI

• PRIDE
  1. PXD066935
     1. Label: PRIDE project
     2. Name: Testican-2 interaction with the extracellular matrix and podocyte protection