Effects of Perfusion Pressures on Podocyte Loss in the Isolated Perfused Mouse Kidney.
Glomerular hypertension; Glomerular hyperfiltration; Mechanical stress; Progression; CKD; Chronic kidney disease
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
14 Apr 2021
14 Apr 2021
Historique:
accepted:
30
03
2021
entrez:
14
4
2021
pubmed:
15
4
2021
medline:
25
8
2021
Statut:
ppublish
Résumé
Podocytes are lost in most glomerular diseases, leading to glomerulosclerosis and progressive kidney disease. It is generally assumed, that podocytes are exposed to the filtration flow and thus to significant shear forces driving their detachment from the glomerular basement membrane (GBM). In this context, foot process effacement has been proposed as potential adaptive response to increase adhesion of podocytes to the GBM. We have tested these hypotheses using optical clearing and high-resolution 3-dimensional morphometric analysis in the isolated perfused murine kidney. We investigated the dynamics of podocyte detachment at different perfusion pressures (50, 300 and more than 450 mmHg) in healthy young or old mice (20 vs. 71 weeks of age), or mice injected with anti-GBM serum to induce global foot process effacement. Results show that healthy podocytes in young mice are tightly attached onto the GBM and even supramaximal pressures did not cause significant detachment. Compared to young mice, in aged mice and mice with anti-GBM nephritis and foot process effacement, gradual progressive loss of podocytes had occurred already before perfusion. High perfusion pressures resulted in a relatively minor additional loss of podocytes in aged mice. In mice with anti-GBM nephritis significant additional podocyte loss occurred at this early time point when increasing perfusion pressures to 300 mmHg or higher. This work provides the first experimental evidence that podocytes are extraordinarily resistant to acutely increased perfusion pressures in an ex vivo isolated kidney perfusion model. Only in glomerular disease, significant numbers of injured podocytes detached following acute increases in perfusion pressure.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
Podocytes are lost in most glomerular diseases, leading to glomerulosclerosis and progressive kidney disease. It is generally assumed, that podocytes are exposed to the filtration flow and thus to significant shear forces driving their detachment from the glomerular basement membrane (GBM). In this context, foot process effacement has been proposed as potential adaptive response to increase adhesion of podocytes to the GBM.
METHODS
METHODS
We have tested these hypotheses using optical clearing and high-resolution 3-dimensional morphometric analysis in the isolated perfused murine kidney. We investigated the dynamics of podocyte detachment at different perfusion pressures (50, 300 and more than 450 mmHg) in healthy young or old mice (20 vs. 71 weeks of age), or mice injected with anti-GBM serum to induce global foot process effacement.
RESULTS
RESULTS
Results show that healthy podocytes in young mice are tightly attached onto the GBM and even supramaximal pressures did not cause significant detachment. Compared to young mice, in aged mice and mice with anti-GBM nephritis and foot process effacement, gradual progressive loss of podocytes had occurred already before perfusion. High perfusion pressures resulted in a relatively minor additional loss of podocytes in aged mice. In mice with anti-GBM nephritis significant additional podocyte loss occurred at this early time point when increasing perfusion pressures to 300 mmHg or higher.
CONCLUSION
CONCLUSIONS
This work provides the first experimental evidence that podocytes are extraordinarily resistant to acutely increased perfusion pressures in an ex vivo isolated kidney perfusion model. Only in glomerular disease, significant numbers of injured podocytes detached following acute increases in perfusion pressure.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-12Subventions
Organisme : German Ministry for Science and Education
ID : BMBF 01GM1518A, Heisenberg Professorship MO 1082/8-1
Pays : Germany
Organisme : Deutsche Forschungsgemeinsschaft (DFG)
ID : TP17 SFB/TRR 57, SFB/TRR219, B03755/3-1, B03755/9-1, B03755/13-1, CRU5011-SP05, CRU5011-SP03
Pays : Germany
Organisme : RWTH Aachen University
ID : START grant (19/21), Clinician scientist Scholarship
Pays : Germany
Organisme : German Society of Nephrology (DGfN)
Pays : Germany
Organisme : Else Kröner-Fresenius Stiftung
Pays : Germany
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicting interests.