Elevated glucose represses lysosomal and mTOR-related genes in renal epithelial cells composed of progenitor CD133+ cells.
AC133 Antigen
/ analysis
Cells, Cultured
Diabetic Nephropathies
/ genetics
Epithelial Cells
/ cytology
Gene Expression Regulation
Gene Regulatory Networks
Glucose
/ metabolism
Humans
Hyperglycemia
/ genetics
Kidney Tubules
/ cytology
Lysosomes
/ genetics
Stem Cells
/ cytology
TOR Serine-Threonine Kinases
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
19
09
2020
accepted:
23
02
2021
entrez:
25
3
2021
pubmed:
26
3
2021
medline:
15
10
2021
Statut:
epublish
Résumé
Hyperglycemia is one of the major health concern in many parts of the world. One of the serious complications of high glucose levels is diabetic nephropathy. The preliminary microarray study performed on primary human renal tubular epithelial (hRTE) cells exposed to high glucose levels showed a significant downregulation of mTOR as well as its associated genes as well as lysosomal genes. Based on this preliminary data, the expression of various lysosomal genes as well as mTOR and its associated genes were analyzed in hRTE cells exposed to 5.5, 7.5, 11 and 16 mM glucose. The results validated the microarray analysis, which showed a significant decrease in the mRNA as well as protein expression of the selected genes as the concentration of glucose increased. Co-localization of lysosomal marker, LAMP1 with mTOR showed lower expression of mTOR as the glucose concentration increased, suggesting decrease in mTOR activity. Although the mechanism by which glucose affects the regulation of lysosomal genes is not well known, our results suggest that high levels of glucose may lead to decrease in mTOR expression causing the cells to enter an anabolic state with subsequent downregulation of lysosomal genes.
Identifiants
pubmed: 33764985
doi: 10.1371/journal.pone.0248241
pii: PONE-D-20-29587
pmc: PMC7993790
doi:
Substances chimiques
AC133 Antigen
0
PROM1 protein, human
0
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0248241Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103442
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM113123
Pays : United States
Déclaration de conflit d'intérêts
The authors declared that no competing interests exist.
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