Unraveling the role of podocyte turnover in glomerular aging and injury
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Unraveling the role of podocyte turnover in glomerular aging and injury. / Wanner, Nicola; Hartleben, Björn; Herbach, Nadja; Goedel, Markus; Stickel, Natalie; Zeiser, Robert; Walz, Gerd; Moeller, Marcus J; Grahammer, Florian; Huber, Tobias B.
In: J AM SOC NEPHROL, Vol. 25, No. 4, 04.2014, p. 707-16.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Unraveling the role of podocyte turnover in glomerular aging and injury
AU - Wanner, Nicola
AU - Hartleben, Björn
AU - Herbach, Nadja
AU - Goedel, Markus
AU - Stickel, Natalie
AU - Zeiser, Robert
AU - Walz, Gerd
AU - Moeller, Marcus J
AU - Grahammer, Florian
AU - Huber, Tobias B
PY - 2014/4
Y1 - 2014/4
N2 - Podocyte loss is a major determinant of progressive CKD. Although recent studies showed that a subset of parietal epithelial cells can serve as podocyte progenitors, the role of podocyte turnover and regeneration in repair, aging, and nephron loss remains unclear. Here, we combined genetic fate mapping with highly efficient podocyte isolation protocols to precisely quantify podocyte turnover and regeneration. We demonstrate that parietal epithelial cells can give rise to fully differentiated visceral epithelial cells indistinguishable from resident podocytes and that limited podocyte renewal occurs in a diphtheria toxin model of acute podocyte ablation. In contrast, the compensatory programs initiated in response to nephron loss evoke glomerular hypertrophy, but not de novo podocyte generation. In addition, no turnover of podocytes could be detected in aging mice under physiologic conditions. In the absence of podocyte replacement, characteristic features of aging mouse kidneys included progressive accumulation of oxidized proteins, deposits of protein aggregates, loss of podocytes, and glomerulosclerosis. In summary, quantitative investigation of podocyte regeneration in vivo provides novel insights into the mechanism and capacity of podocyte turnover and regeneration in mice. Our data reveal that podocyte generation is mainly confined to glomerular development and may occur after acute glomerular injury, but it fails to regenerate podocytes in aging kidneys or in response to nephron loss.
AB - Podocyte loss is a major determinant of progressive CKD. Although recent studies showed that a subset of parietal epithelial cells can serve as podocyte progenitors, the role of podocyte turnover and regeneration in repair, aging, and nephron loss remains unclear. Here, we combined genetic fate mapping with highly efficient podocyte isolation protocols to precisely quantify podocyte turnover and regeneration. We demonstrate that parietal epithelial cells can give rise to fully differentiated visceral epithelial cells indistinguishable from resident podocytes and that limited podocyte renewal occurs in a diphtheria toxin model of acute podocyte ablation. In contrast, the compensatory programs initiated in response to nephron loss evoke glomerular hypertrophy, but not de novo podocyte generation. In addition, no turnover of podocytes could be detected in aging mice under physiologic conditions. In the absence of podocyte replacement, characteristic features of aging mouse kidneys included progressive accumulation of oxidized proteins, deposits of protein aggregates, loss of podocytes, and glomerulosclerosis. In summary, quantitative investigation of podocyte regeneration in vivo provides novel insights into the mechanism and capacity of podocyte turnover and regeneration in mice. Our data reveal that podocyte generation is mainly confined to glomerular development and may occur after acute glomerular injury, but it fails to regenerate podocytes in aging kidneys or in response to nephron loss.
KW - Aging
KW - Animals
KW - Flow Cytometry
KW - Hypertrophy
KW - Kidney Glomerulus
KW - Mice
KW - Podocytes
KW - Regeneration
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1681/ASN.2013050452
DO - 10.1681/ASN.2013050452
M3 - SCORING: Journal article
C2 - 24408871
VL - 25
SP - 707
EP - 716
JO - J AM SOC NEPHROL
JF - J AM SOC NEPHROL
SN - 1046-6673
IS - 4
ER -