Effects of Perfusion Pressures on Podocyte Loss in the Isolated Perfused Mouse Kidney

TY - JOUR

T1 - Effects of Perfusion Pressures on Podocyte Loss in the Isolated Perfused Mouse Kidney

AU - Strieder, Thiago

AU - Puelles, Victor G

AU - Vogt, Michael

AU - Buhl, Eva M

AU - Saritas, Turgay

AU - Hausmann, Ralf

AU - Sterzer, Viktor

AU - Leuchtle, Katja

AU - Boor, Peter

AU - Floege, Jürgen

AU - Moeller, Marcus J

AU - Stamellou, Eleni

N1 - © Copyright by the Author(s). Published by Cell Physiol Biochem Press.

PY - 2021/4/14

Y1 - 2021/4/14

N2 - BACKGROUND/AIMS: 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: 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 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: 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.

AB - BACKGROUND/AIMS: 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: 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 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: 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.

KW - Aging

KW - Animals

KW - Cell Adhesion

KW - Cell Survival

KW - Female

KW - Glomerular Basement Membrane/cytology

KW - Kidney Diseases/pathology

KW - Male

KW - Mice

KW - Perfusion

KW - Podocytes/cytology

KW - Pressure

U2 - 10.33594/000000355

DO - 10.33594/000000355

M3 - SCORING: Journal article

C2 - 33851800

VL - 55

SP - 1

EP - 12

JO - CELL PHYSIOL BIOCHEM

JF - CELL PHYSIOL BIOCHEM

SN - 1015-8987

IS - S4

ER -