PXD007828

PXD007828 is an original dataset announced via ProteomeXchange.

Title	PPARs and c-Myc regulate metabolism of renal tubules
Description	Different segments of renal tubules have distinct metabolic features and functions, and defective metabolism in renal tubules is involved in the pathobiology of kidney diseases. However, the mechanisms underlying the metabolic regulation in renal tubules remain to be defined. We demonstrated that the renal proximal tubule (PT) has high expression of fatty acid and lipid metabolism enzymes, which is transcriptionally upregulated by abundantly expressed peroxisome proliferator-activated receptor (PPAR)/γ to support active lipid metabolism. In contrast, the renal distal tubule (DT) has elevated glycolytic enzyme expression corresponding with high rates of glycolysis, and this increased expression is mediated by abundantly expressed c-Myc. In addition, Nrf2 upregulated glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-dependent malic enzyme 1 expression for NADPH production and antioxidation in the DT. Highly expressed PPARγ transcriptionally enhanced expression of the protease iRhom2 in the PT, which suppressed epidermal growth factor (EGF) expression and secretion, inhibiting EGF receptor activation-dependent glycolytic gene expression and maintaining the low level of glycolysis. PPARγ inhibition reduced iRhom2 expression and increased EGF and GLUT1 expression in the PT in mice, resulting in hypertrophy of renal tubules and inhibited kidney functions, which can be rescued by inhibition of glycolysis via treatment with 2-deoxy-D-glucose. These findings delineate instrumental molecular mechanisms underlying the active lipid metabolism and suppressed glycolysis in the PT and active glycolysis in the DT and reveal critical roles for PPARs and c-Myc in maintaining metabolic homeostasis in the kidney
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:40:56.885.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhongshi Lyu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-25 01:51:37	ID requested
1	2018-11-15 14:10:56	announced
⏵ 2	2024-10-22 04:41:05	announced	2024-10-22: Updated project metadata.

10.1016/j.ebiom.2018.10.072;

Lyu Z, Mao Z, Li Q, Xia Y, Liu Y, He Q, Wang Y, Zhao H, Lu Z, Zhou Q, maintains the metabolic heterogeneity and homeostasis of renal tubules. EBioMedicine, 38():178-190(2018) [pubmed]

curator keyword: Biological

submitter keyword: PPARγ

PPAR

c-Myc

Nrf2

lipid metabolism

glycolysis

renal proximal tubules

renal distal tubules

kidney

Qin Zhou
contact affiliation	The Division of Molecular Nephrology, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, The School of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of China.
contact email	zhouqin@cqmu.edu.cn
lab head
Zhongshi Lyu
contact affiliation	Peking University
contact email	zhongshilyu@163.com
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/2018/11/PXD007828

PRIDE project URI

• PRIDE
  1. PXD007828
     1. Label: PRIDE project
     2. Name: PPARs and c-Myc regulate metabolism of renal tubules