The podocyte-specific knockout of palladin in mice with a 129 genetic background affects podocyte morphology and the expression of palladin interacting proteins.
Actin Cytoskeleton
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Cytoskeletal Proteins
/ genetics
Genetic Background
Homeodomain Proteins
/ genetics
Kidney
/ metabolism
LIM Domain Proteins
/ genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microfilament Proteins
/ genetics
Phosphorylation
Podocytes
/ cytology
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:
16
06
2021
accepted:
18
11
2021
entrez:
8
12
2021
pubmed:
9
12
2021
medline:
7
1
2022
Statut:
epublish
Résumé
Proper and size selective blood filtration in the kidney depends on an intact morphology of podocyte foot processes. Effacement of interdigitating podocyte foot processes in the glomeruli causes a leaky filtration barrier resulting in proteinuria followed by the development of chronic kidney diseases. Since the function of the filtration barrier is depending on a proper actin cytoskeleton, we studied the role of the important actin-binding protein palladin for podocyte morphology. Podocyte-specific palladin knockout mice on a C57BL/6 genetic background (PodoPalldBL/6-/-) were back crossed to a 129 genetic background (PodoPalld129-/-) which is known to be more sensitive to kidney damage. Then we analyzed the morphological changes of glomeruli and podocytes as well as the expression of the palladin-binding partners Pdlim2, Lasp-1, Amotl1, ezrin and VASP in 6 and 12 months old mice. PodoPalld129-/- mice in 6 and 12 months showed a marked dilatation of the glomerular tuft and a reduced expression of the mesangial marker protein integrin α8 compared to controls of the same age. Furthermore, ultrastructural analysis showed significantly more podocytes with morphological deviations like an enlarged sub-podocyte space and regions with close contact to parietal epithelial cells. Moreover, PodoPalld129-/- of both age showed a severe effacement of podocyte foot processes, a significantly reduced expression of pLasp-1 and Pdlim2, and significantly reduced mRNA expression of Pdlim2 and VASP, three palladin-interacting proteins. Taken together, the results show that palladin is essential for proper podocyte morphology in mice with a 129 background.
Identifiants
pubmed: 34879092
doi: 10.1371/journal.pone.0260878
pii: PONE-D-21-19473
pmc: PMC8654177
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Cytoskeletal Proteins
0
Homeodomain Proteins
0
LIM Domain Proteins
0
Lasp1 protein, mouse
0
Microfilament Proteins
0
Pdlim2 protein, mouse
0
palladin protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0260878Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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