Hemicentin 1 influences podocyte dynamic changes in glomerular diseases.

Details

Serval ID
serval:BIB_C10F843FD413
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hemicentin 1 influences podocyte dynamic changes in glomerular diseases.
Journal
American Journal of Physiology. Renal physiology
Author(s)
Toffoli B., Zennaro C., Winkler C., Giordano Attianese GMP, Bernardi S., Carraro M., Gilardi F., Desvergne B.
ISSN
1522-1466 (Electronic)
ISSN-L
1931-857X
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
314
Number
6
Pages
F1154-F1165
Language
english
Abstract
Different complex mechanisms control the morphology of podocyte foot processes and their interactions with the underlying basement membrane. Injuries to this system often cause glomerular dysfunction and albuminuria. The present study aimed at identifying early markers of glomerular damage in diabetic nephropathy. For this purpose, we performed a microarray analysis on kidneys of 3-wk-old peroxisome proliferator-activated receptor-γ (PPARγ)-null and AZIP/F1 mice, which are two models of diabetic nephropathy due to lipodystrophy. This was followed by functional annotation of the enriched clusters of genes. One of the significant changes in the early stages of glomerular damage was the increase of hemicentin 1 (HMCN1). Its expression and distribution were then studied by real-time PCR and immunofluorescence in various models of glomerular damage and on podocyte cell cultures. HMCN1 progressively increased in the glomeruli of diabetic mice, according to disease severity, as well as in puromycin aminonucleoside (PA)-treated rats. Studies on murine and human podocytes showed an increased HMCN1 deposition upon different pathological stimuli, such as hyperglycemia, transforming growth factor-β (TGF-β), and PA. In vitro silencing studies showed that HMCN1 mediated the rearrangements of podocyte cytoskeleton induced by TGF-β. Finally, we demonstrated an increased expression of HMCN1 in the kidneys of patients with proteinuric nephropathies. In summary, our studies identified HMCN1 as a new molecule involved in the dynamic changes of podocyte foot processes. Its increased expression associated with podocyte dysfunction points to HMCN1 as a possible marker for the early glomerular damage occurring in different proteinuric nephropathies.
Keywords
F-actin, diabetic nephropathy, focal segmental glomerulosclerosis, glomerular basement membrane, microarray analysis
Pubmed
Web of science
Create date
03/03/2018 14:15
Last modification date
20/08/2019 16:35
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