PXD066759-1

PXD066759 is an original dataset announced via ProteomeXchange.

Title	Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet
Description	Female Lrp2 (megalin) f/f mice were bred with male Ndrg1-Cre ERT2 +/0 mice to develop PTC-LRP2 +/+ and PTC-LRP2-/- littermates. To study atherosclerosis, all mice were bred to an LDL receptor -/- background and fed a Western diet to induce atherosclerosis. PTC-specific megalin deletion did not attenuate atherosclerosis in LDL receptor -/- mice in either sex. Serendipitously, we discovered that PTC-specific megalin deletion led to interstitial infiltration of CD68+ cells and tubular atrophy. The pathology was only evident in male PTC-LRP2 -/- mice fed the Western diet, but not in mice fed a normal laboratory diet. Renal pathologies were also observed in male PTC-LRP2 -/- mice in an LDL receptor +/+ background fed the same Western diet, demonstrating that the renal pathologies were dependent on diet and not hypercholesterolemia. In contrast, female PTC-LRP2 -/- mice had no apparent renal pathologies. Urine proteomics analysis discovered that many megalin ligands were increased in urine of male PTC-LRP2 -/- mice, compared to their PTC-LRP2 +/+ littermates.
HostingRepository	PRIDE
AnnounceDate	2025-10-24
AnnouncementXML	Submission_2025-10-24_06:07:45.731.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD066759
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Abigail Burrows Franco
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-30 06:41:23	ID requested
⏵ 1	2025-10-24 06:07:46	announced

Amioka N, Franklin MK, Kukida M, Zhu L, Moorleghen JJ, Howatt DA, Katsumata Y, Mullick AE, Yanagita M, Martinez-Irizarry MM, Sandoval RM, Dunn KW, Sawada H, Daugherty A, Lu HS, Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet. Arterioscler Thromb Vasc Biol, 45(1):74-89(2025) [pubmed]

10.1161/atvbaha.124.321366;

10.6019/PXD066759;

ProteomeXchange project tag: Cardiovascular (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: atherosclerosis, megalin, tubulointerstitial, nephrititis, renal, mice

Hong S Lu
contact affiliation	Saha Cardiovascular Research Center and Saha Aortic Center Department of Physiology University of Kentucky Lexington, KY USA
contact email	Hong.Lu@uky.edu
lab head
Abigail Burrows Franco
contact affiliation	Research Mass Spectrometry and Proteomics Core University of Kentucky
contact email	abigail.burrows@uky.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066759
     1. Label: PRIDE project
     2. Name: Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet