Subscribe to RSS
DOI: 10.1055/s-0030-1255142
© Georg Thieme Verlag KG Stuttgart · New York
Neue Erkenntnisse zur glomerulären Struktur
Novel insights into the glomerular structurePublication History
eingereicht: 31.1.2010
akzeptiert: 20.5.2010
Publication Date:
08 June 2010 (online)

Zusammenfassung
Während der letzten Jahre hat es bedeutende Forschritte im Verständnis des Aufbaus und der Pathomechanismen des renalen Glomerulus gegeben. In dieser Übersichtsarbeit wird eine Auswahl neuer Aspekte beleuchtet: 1.) Die Funktionsweise der glomerulären Filtrationsbarriere ist bis heute noch nicht gänzlich aufgeklärt, obwohl mittlerweile der anatomische Aufbau auch auf molekularer Ebene gut bekannt ist. 2.) Im Glomerulus vermittelt vascular endothelial growth factor (VEGF) ein von den Podozyten ausgehendes, räumliches Signal, das entscheidend den Aufbau des Glomerulus beeinflusst. 3.) Die Theorie des subpodocyte space liefert eine neue Erklärung für den effektiven Rücktransport von VEGF gegen den Filtrationsstrom von den Podozyten zu den Endothelzellen. 4.) Neu entwickelte transgene Mausmodelle haben nach den Podozyten nun auch die Parietalzellen einer systematischen funktionellen Erforschung zugänglich gemacht. Parietalzellen stellen möglicherweise eine intrarenale Progenitorzellpopulation für die Regeneration von Podozyten dar. 5.) Parietalzellen spielen eine bislang unterschätzte Rolle bei verschiedenen glomerulären Erkrankungen. So werden zelluläre Halbmonde im Rahmen einer rapid progressiven Glomerulonephritis vor allem von glomerulären Parietalzellen ausgebildet.
Abstract
In recent years, significant progress has been made in understanding the structure and pathomechanisms of the glomerulus of the kidney. Some of these more recent advances and open questions are discussed in this review: 1.) The functioning of the glomerular filter still remains incompletely understood, although the microanatomy and molecular biology of the glomerular filter has been investigated in great detail. 2.) Vascular endothelial growth factor (VEGF) has been shown to mediate spacial clues that are essential for the polarized distribution of the cells within the glomerulus. 3.) A novel theory of the subpodocyte space offers a novel explanation for the flux of VEGF from the podocytes against the bulk flow of the filtrate to the glomerular endothelial cells. 4.) Novel transgenic mouse models have enabled us to investigate the functional role not only of podocytes but more recently also of parietal cells which might serve as an intrarenal progenitor cell population. 5.) Parietal cells play a so far under-recognized role in various glomerular diseases. In rapid progressive glomerulonephritis, cellular crescents originate predominantly from parietal cells.
Schlüsselwörter
Glomerulus - Filtrationsbarriere - VEGF - Parietalzellen - Podozyten
Keywords
glomerulus - filtration barrier - VEGF - parietal cells - podocytes
Literatur
- 1
Appel D, Kershaw D B, Smeets B. et al .
Recruitment of podocytes from glomerular
parietal epithelial cells.
J Am Soc Nephrol.
2009;
20
333-343
MissingFormLabel
- 2
Comper W D, Hilliard L M, Nikolic-Paterson D J, Russo L M.
Disease-dependent mechanisms of albuminuria.
Am J
Physiol Renal Physiol.
2008;
295
F1589-600
MissingFormLabel
- 3
Deen W M, Bohrer M P, Brenner B M.
Macromolecule transport across glomerular
capillaries: application of pore theory.
Kidney Int.
1979;
16
353-365
MissingFormLabel
- 4
Duffield J S, Tipping P G, Kipari T. et al .
Conditional ablation of macrophages halts
progression of crescentic glomerulonephritis.
Am J Pathol.
2005;
167
1207-1219
MissingFormLabel
- 5
Eremina V, Jefferson J A, Kowalewska J. et al .
VEGF inhibition and renal thrombotic microangiopathy.
N Engl J Med.
2008;
358
1129-1136
MissingFormLabel
- 6
Eremina V, Sood M, Haigh J. et
al .
Glomerular-specific alterations of VEGF-A expression
lead to distinct congenital and acquired renal diseases.
J
Clin Invest.
2003;
111
707-716
MissingFormLabel
- 7
Esser S, Wolburg K, Wolburg H, Breier G, Kurzchalia T, Risau W.
Vascular endothelial growth
factor induces endothelial fenestrations in vitro.
J Cell
Biol.
1998;
140
947-959
MissingFormLabel
- 8
Fries J W, Sandstrom D J, Meyer T W, Rennke H G.
Glomerular
hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis
in the rat.
Lab Invest.
1989;
60
205-218
MissingFormLabel
- 9
Fujigaki Y, Nagase M, Kobayasi S, Hidaka S, Shimomura M, Hishida A.
Intra-GBM site of the
functional filtration barrier for endogenous proteins in rats.
Kidney Int.
1993;
43
567-574
MissingFormLabel
- 10
Gibson I W, Gardiner D S, Downie I, Downie T T, More I A, Lindop G B.
A
comparative study of the glomerular peripolar cell and the renin-secreting cell
in twelve mammalian species.
Cell Tissue Res.
1994;
277
385-390
MissingFormLabel
- 11
Hakroush S, Moeller M J, Theilig F. et al .
Effects of increased renal tubular vascular
endothelial growth factor (VEGF) on fibrosis, cyst formation, and
glomerular disease.
Am J Pathol.
2009;
175
1883-1895
MissingFormLabel
- 12
Haraldsson B, Barisoni L, Quaggin S E.
Reply to: VEGF inhibition and renal thrombotic microangiopathy.
New Engl J Med.
2008;
359
205-207
MissingFormLabel
- 13
Haraldsson B, Nystrom J, Deen W M.
Properties of the glomerular barrier and mechanisms of proteinuria.
Physiol Rev.
2008;
88
451-487
MissingFormLabel
- 14
Huber T B, Benzing T.
The slit diaphragm:
a signaling platform to regulate podocyte function.
Curr
Opin Nephrol Hypertens.
2005;
14
211-216
MissingFormLabel
- 15
Kamba T, Tam B Y, Hashizume H. et al .
VEGF-dependent plasticity of fenestrated
capillaries in the normal adult microvasculature.
Am J Physiol
Heart Circ Physiol.
2006;
290
H560-576
MissingFormLabel
- 16 Kriz W, Kaissling B. Structural organization
of the mammalian kidney. In: Seldin DW, Giebisch G The
Kidney: Physiology and Pathophysiology. New York: Raven Press; 1992: 707-777
MissingFormLabel
- 17
Kriz W, LeHir M.
Pathways to nephron loss starting
from glomerular diseases-insights from animal models.
Kidney
Int.
2005;
67
404-419
MissingFormLabel
- 18
Kriz W, Lemley K V.
The role of the
podocyte in glomerulosclerosis.
Curr Opin Nephrol Hypertens.
1999;
8
489-497
MissingFormLabel
- 19
LeHir M, Besse-Eschmann V.
A novel mechanism
of nephron loss in a murine model of crescentic glomerulonephritis.
Kidney Int.
2003;
63
591-599
MissingFormLabel
- 20
Macconi D, Sangalli F, Bonomelli M. et al .
Podocyte repopulation contributes to regression
of glomerular injury induced by ACE inhibition.
Am J Pathol.
2009;
174
797-807
MissingFormLabel
- 21
Moeller M J, Kovari I A, Holzman L B.
Evaluation of a new tool for exploring podocyte
biology: mouse Nphs1 5’ flanking region drives LacZ expression
in podocytes.
J Am Soc Nephrol.
2000;
11
2306-2314
MissingFormLabel
- 22
Moeller M J, Sanden S K, Soofi A, Wiggins R C, Holzman L B.
Podocyte-specific expression of cre recombinase
in transgenic mice.
Genesis.
2003;
35
39-42
MissingFormLabel
- 23
Moeller M J, Soofi A, Braun G S. et al .
Protocadherin FAT1 binds Ena/VASP
proteins and is necessary for actin dynamics and cell polarization.
EMBO J.
2004;
23
3769-3779
MissingFormLabel
- 24
Moeller M J, Soofi A, Hartmann I. et al .
Podocytes populate cellular crescents in
a murine model of inflammatory glomerulonephritis.
J Am Soc
Nephrol.
2004;
15
61-67
MissingFormLabel
- 25
Neal C R, Muston P R, Njegovan D. et al .
Glomerular filtration into the subpodocyte
space is highly restricted under physiological perfusion conditions.
Am J Physiol Renal Physiol.
2007;
293
F1787-1798
MissingFormLabel
- 26
Pabst R, Sterzel R B.
Cell renewal of
glomerular cell types in normal rats. An autoradiographic analysis.
Kidney Int.
1983;
24
626-31
MissingFormLabel
- 27
Remuzzi A, Gagliardini E, Sangalli F. et al .
ACE inhibition reduces glomerulosclerosis
and regenerates glomerular tissue in a model of progressive renal
disease.
Kidney Int.
2006;
69
1124-30
MissingFormLabel
- 28
Rippe B, Haraldsson B.
Transport of macromolecules
across microvascular walls: the two-pore theory.
Physiol
Rev.
1994;
74
163-219
MissingFormLabel
- 29
Ronconi E, Sagrinati C, Angelotti M L. et al .
Regeneration of glomerular podocytes
by human renal progenitors.
J Am Soc Nephrol.
2009;
20
322-332
MissingFormLabel
- 30
Rostgaard J, Qvortrup K.
Sieve plugs in fenestrae
of glomerular capillaries – site of the filtration barrier?.
Cells Tissues Organs.
2002;
170
132-138
MissingFormLabel
- 31
Russo L M, Sandoval R M, McKee M. et al .
The normal kidney filters nephrotic levels
of albumin retrieved by proximal tubule cells: retrieval is disrupted
in nephrotic states.
Kidney Int.
2007;
71
504-513
MissingFormLabel
- 32
Ryan G B, Karnovsky M J.
Distribution
of endogenous albumin in the rat glomerulus: role of hemodynamic
factors in glomerular barrier function.
Kidney Int.
1976;
9
36-45
MissingFormLabel
- 33
Shigehara T, Zaragoza C, Kitiyakara C. et al .
Inducible podocyte-specific gene expression
in transgenic mice.
J Am Soc Nephrol.
2003;
14
1998-2003
MissingFormLabel
- 34
Smeets B, Angelotti M L, Rizzo P. et al .
Renal progenitor cells contribute to hyperplastic
lesions of podocytopathies and crescentic glomerulonephritis.
J Am Soc Nephrol.
2009;
20
2593-2603
MissingFormLabel
- 35
Smeets B, Uhlig S, Fuss A. et
al .
Tracing the origin of glomerular extracapillary
lesions from parietal epithelial cells.
J Am Soc Nephrol.
2009;
20
2604-2615
MissingFormLabel
- 36
Smithies O.
Why the kidney glomerulus does not clog: a gel permeation/diffusion
hypothesis of renal function.
Proc Nat Acad Sci.
2003;
100
4108-4113
MissingFormLabel
- 37
Tryggvason K, Wartiovaara J.
How does the kidney
filter plasma?.
Physiology (Bethesda).
2005;
20
96-101
MissingFormLabel
- 38
Wartiovaara J, Ofverstedt L G, Khoshnoodi J. et al .
Nephrin strands contribute
to a porous slit diaphragm scaffold as revealed by electron tomography.
J Clin Invest.
2004;
114
1475-1483
MissingFormLabel
- 39
Wharram B L, Goyal M, Wiggins J E. et al .
Podocyte depletion causes glomerulosclerosis:
diphtheria toxin-induced podocyte depletion in rats expressing human
diphtheria toxin receptor transgene.
J Am Soc Nephrol.
2005;
16
2941-2952
MissingFormLabel
- 40
Wolgast M, Kallskog O, Wahlstrom H.
Characteristics of the glomerular capillary membrane of the
rat kidney as a hydrated gel. II. On the validity of the model.
Acta Physiol Scand.
1996;
158
225-232
MissingFormLabel
- 41
Wong M A, Cui S, Quaggin S E.
Identification and characterization of a glomerular-specific
promoter from the human nephrin gene.
Am J Physiol Renal
Physiol.
2000;
279
F1027-1032
MissingFormLabel
PD Dr. med. Marcus J. Moeller
Medizinische Klinik 2, Nephrologie und Klinische Immunologie, Universitätsklinikum
der RWTH Aachen
Pauwelsstr. 30
52074 Aachen
Email: mmoeller@ukaachen.de