Krϋppel‐like factor 15 suppresses renal glomerular mesangial cell proliferation via enhancing P53 SUMO1 conjugation

Mesangial cell (MC) proliferation is a key pathological feature in a number of common human renal diseases, including mesangial proliferative nephritis and diabetic nephropathies. Knowledge of MC responses to pathological stimuli is crucial to the understanding of these disease processes. We previou...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular and molecular medicine 2021-06, Vol.25 (12), p.5691-5706
Main Authors: Wu, Lingling, Li, Ou, Zhu, Fengge, Wang, Xu, Chen, Pu, Cai, Guangyan, Chen, Xiangmei, Hong, Quan
Format: Article
Language:English
Subjects:
Antibodies
Binding sites
Cell cycle
Cell proliferation
Diabetes mellitus
Glucose
Kidney diseases
Kidneys
KLF15
Labeling
Laboratory animals
Mass spectrometry
Mesangial cell proliferation
Nephritis
Original
P53
p53 Protein
Peptides
Proliferative kidney disease
Proteins
Scientific imaging
Software
SUMO protein
SUMO1
Ubiquitin
Zinc finger proteins
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mesangial cell (MC) proliferation is a key pathological feature in a number of common human renal diseases, including mesangial proliferative nephritis and diabetic nephropathies. Knowledge of MC responses to pathological stimuli is crucial to the understanding of these disease processes. We previously determined that Krϋppel‐like factor 15 (KLF15), a kidney‐enriched zinc‐finger transcription factor, was required for inhibition of MC proliferation. In the present study, we investigated the direct target gene and the underlying mechanism by which KLF15 regulated mesangial proliferation. First, we screened small ubiquitin‐related modifier 1 (SUMO1) as the direct transcriptional target of KLF15 and validated this finding with ChIP‐PCR and luciferase assays. Furthermore, we demonstrated that overexpressing KLF15 or SUMO1 enhanced the stability of P53, which blocked the cell cycle of human renal MCs (HRMCs) and therefore abolished cell proliferation. Conversely, knockdown of SUMO1 in HRMCs, even those overexpressed with KLF15, could not inhibit HRMC proliferation rates and increase SUMOylation of P53. Finally, the results showed that the levels of SUMOylated P53 in the kidney cortices of anti‐Thy 1 model rats were decreased during proliferation periods. These findings reveal the critical mechanism by which KLF15 targets SUMO1 to mediate the proliferation of MCs.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.16583