Parietal epithelial cell differentiation to a podocyte fate in the aged mouse kidney

被引：26

作者：

Kaverina, Natalya, V ^{[1
]}

Eng, Diana G. ^{[1
]}

Miner, Jeffrey H. ^{[2
]}

Pippin, Jeffrey W. ^{[1
]}

Shankland, Stuart J. ^{[1
]}

机构：

[1] Univ Washington, Div Nephrol, Seattle, WA 98195 USA

[2] Washington Univ, Div Nephrol, Sch Med, St Louis, MO 63110 USA

来源：

AGING-US | 2020年 / 12卷 / 17期

关键词：

reporter; tdTomato; EGFP; differentiation; Bowman's capsule; DE-NOVO EXPRESSION; RENIN LINEAGE; EXPERIMENTAL FSGS; PROGENITOR CELLS; VEGF-A; DEPLETION; GLOMERULOSCLEROSIS; REGENERATION; PROTEINS; PROLIFERATION;

D O I：

10.18632/aging.103788

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Healthy aging is typified by a progressive and absolute loss of podocytes over the lifespan of animals and humans. To test the hypothesis that a subset of glomerular parietal epithelial cell (PEC) progenitors transition to a podocyte fate with aging, dual reporter PEC-rtTA/LC1/tdTomato/Nphs1-FLPo/FRT-EGFP mice were generated. PECs were inducibly labeled with a tdTomato reporter, and podocytes were constitutively labeled with an EGFP reporter. With advancing age (14 and 24 months) glomeruli in the juxta-medullary cortex (JMC) were more severely injured than those in the outer cortex (OC). In aged mice (24m), injured glomeruli with lower podocyte number (41% decrease), showed more PEC migration and differentiation to a podocyte fate than mildly injured or healthy glomeruli. PECs differentiated to a podocyte fate had ultrastructural features of podocytes and co-expressed the podocyte markers podocin, nephrin, p57 and VEGF164, but not markers of mesangial (Perlecan) or endothelial (ERG) cells. PECs differentiated to a podocyte fate did not express CD44, a marker of PEC activation. Taken together, we demonstrate that a subpopulation of PECs differentiate to a podocyte fate predominantly in injured glomeruli in mice of advanced age.

引用

页码：17601 / 17624

页数：24

共 58 条

[1]

ANTICA M, 1994, BLOOD, V84, P111

[2] The Regenerative Potential of Parietal Epithelial Cells in Adult Mice [J].

Berger, Katja ;

Schulte, Kevin ;

Boor, Peter ;

Kuppe, Christoph ;

van Kuppevelt, Toin H. ;

Floege, Juergen ;

Smeets, Bart ;

Moeller, Marcus J. .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2014, 25 (04) :693-705

[3] Volumetric, Nanoscale Optical Imaging of Mouse and Human Kidney via Expansion Microscopy [J].

Chozinski, Tyler J. ;

Mao, Chenyi ;

Halpern, Aaron R. ;

Pippin, Jeffrey W. ;

Shankland, Stuart J. ;

Alpers, Charles E. ;

Najafian, Behzad ;

Vaughan, Joshua C. .

SCIENTIFIC REPORTS, 2018, 8

[4] Detection of renin lineage cell transdifferentiation to podocytes in the kidney glomerulus with dual lineage tracing [J].

Eng, Diana G. ;

Kaverina, Natalya V. ;

Schneider, Remington R. S. ;

Freedman, Benjamin S. ;

Gross, Kenneth W. ;

Miner, Jeffrey H. ;

Pippin, Jeffrey W. ;

Shankland, Stuart J. .

KIDNEY INTERNATIONAL, 2018, 93 (05) :1240-1246

[5] Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis [J].

Eng, Diana G. ;

Sunseri, Maria W. ;

Kaverina, Natalya V. ;

Roeder, Sebastian S. ;

Pippin, Jeffrey W. ;

Shankland, Stuart J. .

KIDNEY INTERNATIONAL, 2015, 88 (05) :999-1012

[6] The role of VEGF-A in glomerular development and function [J].

Eremina, V ;

Quaggin, SE .

CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION, 2004, 13 (01) :9-15

[7] Role of the VEGF-A signaling pathway in the glomerulus: Evidence for crosstalk between components of the glomerular filtration barrier [J].

Eremina, Vera ;

Baelde, Hans J. ;

Quaggin, Susan E. .

NEPHRON PHYSIOLOGY, 2007, 106 (02) :32-37

[8]

Flurkey K, 2006, MOUSE BIOMEDICAL RES

[9] Maintenance of Glomerular Filtration Barrier Integrity Requires Laminin α5 [J].

Goldberg, Seth ;

Adair-Kirk, Tracy L. ;

Senior, Robert M. ;

Miner, Jeffrey H. .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2010, 21 (04) :579-586

[10] Lineage tracing aged mouse kidneys shows lower number of cells of renin lineage and reduced responsiveness to RAAS inhibition [J].

Hamatani, Hiroko ;

Eng, Diana G. ;

Kaverina, Natalya, V ;

Gross, Kenneth W. ;

Freedman, Benjamin S. ;

Pippin, Jeffrey W. ;

Shankland, Stuart J. .

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2018, 315 (01) :F97-F109

← 1 2 3 4 5 6 →