Decreased KAT5 Expression Impairs DNA Repair and Induces Altered DNA Methylation in Kidney Podocytes.
Albuminuria
/ complications
Animals
Cells, Cultured
DNA Breaks, Double-Stranded
DNA Damage
DNA Methylation
DNA Repair
Diabetes Mellitus, Experimental
/ genetics
Diabetic Nephropathies
/ metabolism
Glomerulosclerosis, Focal Segmental
/ complications
Glucose
/ toxicity
Humans
Kidney
/ pathology
Kidney Glomerulus
/ drug effects
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
Lysine Acetyltransferase 5
/ metabolism
Membrane Proteins
/ metabolism
Mice, Inbred C57BL
Mice, Knockout
Podocytes
/ metabolism
Promoter Regions, Genetic
Tamoxifen
/ pharmacology
Trans-Activators
/ metabolism
DNA damage repair
DNA methylation
diabetic nephropathy
podocyte
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
29 01 2019
29 01 2019
Historique:
received:
13
04
2018
revised:
18
11
2018
accepted:
28
12
2018
entrez:
31
1
2019
pubmed:
31
1
2019
medline:
14
3
2020
Statut:
ppublish
Résumé
Altered DNA methylation plays an important role in the onset and progression of kidney disease. However, little is known about how the changes arise in disease states. Here, we report that KAT5-mediated DNA damage repair is essential for the maintenance of kidney podocytes and is associated with DNA methylation status. Podocyte-specific KAT5-knockout mice develop severe albuminuria with increased DNA double-strand breaks (DSBs), increased DNA methylation of the nephrin promoter region, and decreased nephrin expression. Podocyte KAT5 expression is decreased, whereas DNA DSBs and DNA methylation are increased in diabetic nephropathy; moreover, KAT5 restoration by gene transfer attenuates albuminuria. Furthermore, KAT5 decreases DNA DSBs and DNA methylation at the same nephrin promoter region, which indicates that KAT5-mediated DNA repair may be related to DNA methylation status. These results suggest a concept in which an environment of DNA damage repair, which occurs with decreased KAT5, may affect DNA methylation status.
Identifiants
pubmed: 30699357
pii: S2211-1247(19)30005-1
doi: 10.1016/j.celrep.2019.01.005
pii:
doi:
Substances chimiques
Kruppel-Like Factor 4
0
Kruppel-Like Transcription Factors
0
Membrane Proteins
0
Trans-Activators
0
nephrin
0
Tamoxifen
094ZI81Y45
KAT5 protein, human
EC 2.3.1.48
Kat5 protein, mouse
EC 2.3.1.48
Lysine Acetyltransferase 5
EC 2.3.1.48
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1318-1332.e4Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.