PXD038062

PXD038062 is an original dataset announced via ProteomeXchange.

Title	Rat Kidney MS analysis with dehydration and cyclosporine treatment
Description	Background- CINAC-patients can be identified by the recently discovered renal proximal tubular cell lysosomal lesions which are also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy. An alternative hypothesis advocates chronic heat stress/dehydration as the major etiological factor for CINAC. Here, we evaluated in rats to what extent heat stress/dehydration reflects the renal CINAC histopathology in humans. Methods- Wistar rats were divided in 3 groups. Group 1(n=6) had free access to drinking water (control group). Group 2(n=8) was water deprived for 10 hours per 24hr, 5 days/week and placed in an incubator (37°C) for 30 min/hr during water deprivation. Group 3(n=8) underwent daily oral gavage with cyclosporine (40mg/kg body weight). After 28 days kidneys were collected for light- and electron microscopic histopathology and proteomic analysis. Results- Cyclosporine rats developed renal cortical lesions mimicking those of CINAC patients i.e. atrophic proximal tubules with associated tubulo-interstitial fibrosis. PASM staining demonstrated enlarged argyrophilic granules in the affected proximal tubules, identified as lysosomes by LAMP1 immunofluorescent staining. Electron microscopy confirmed the presence of enlarged dysmorphic lysosomes, closely mimicking the dysmorphic lysosomes seen in CINAC-patients. Dehydration was demonstrated by urinary osmolality and fluctuating body weight but showed none of the histological features of CINAC patients. Proteomic analysis confirmed cellular toxicity of cyclosporine, whereas the dehydration group lacked any of these toxicity markers. Conclusion- Dehydration/heat stress alone does not lead to the renal proximal tubular and interstitial lesions as observed in CINAC-patients. The histopathological analogy between CINAC and CNI nephrotoxicity in rats and humans and CINAC supports the toxicological etiology.
HostingRepository	PRIDE
AnnounceDate	2022-11-14
AnnouncementXML	Submission_2022-11-14_05:51:29.425.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	StuartMaudsley
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-09 10:29:24	ID requested
⏵ 1	2022-11-14 05:51:29	announced

Dataset with its publication pending

submitter keyword: kidney MS dehydration cyclosporine

StuartMaudsley
contact affiliation	Receptor Biology Lab, University of Antwerp
contact email	receptorbiologylab@gmail.com
lab head
StuartMaudsley
contact affiliation	Receptor Biology Lab, University of Antwerp
contact email	receptorbiologylab@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038062
     1. Label: PRIDE project
     2. Name: Rat Kidney MS analysis with dehydration and cyclosporine treatment