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Glomerüler Endotel Hastalıklarının Tedavisinde Yeni Ufuklar

New Insight into Treatment of Diseases of Glomerular Endothelium

Journal Name:

  • Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi

Publication Year:

  • 2011
DOI: 
10.5262/tndt.2011.1003.03

Key Words:

Keywords (Original Language):

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Abstract (2. Language): 
The capillary wall of the glomerulus, which is composed of glomerular endothelial cells (GECs), the glomerular basement membrane (GBM), and podocytes, is responsible for the ultrafi ltration of plasma in the kidney. The function of the fenestrated endothelium in fi ltration is poorly understood. On the other hand, the presence of a signifi cant glomerular endothelial glycocalyx implies that the glomerular endothelium signifi cantly contributes to the barrier to macromolecules. Vascular endothelial growth factor (VEGF) is the most important and tightly regulated angiogenic cytokine in the kidney. Studies of fenestration formation have relied on overexpression of VEGF in in vivo models or on in vitro systems where VEGF or pharmacological agents are added exogenously. A greater understanding of the glomerular endothelial cells relevance of in glomerular physiology and pathology naturally raises the question of whether it will be possible to manipulate them therapeutically. For example, promotion of fenestration formation would be desirable in severe preeclampsia to avoid renal failure and may increase GFR in a number of other conditions, including diabetic nephropathy. In the near future, the use of experimental methods will further expand understanding of the pathology of the glomerular fi ltration barrier, and perhaps reveal novel target molecules for the therapy of proteinuric kidney diseases.
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Abstract (Original Language): 
Böbrekten plazmanın ultrafi ltrasyonu, glomerüler endotelyal hücreler, glomerüler bazal membrane ve podositlerden oluşan glomerüler kapiller duvar üzerinden gerçekleşir. Glomerüler endotel hücreleri, sitoplazmaları çok sayıda fenestralarla kaplanmış ve glomerüler fi ltrasyon bariyerinin ileri düzeyde özelleşmiş bir parçasıdır. Bu fi ltrasyon fonksiyonunda fenestraların rolü çok iyi anlaşılamamıştır. Öte yandan glomerüler endotelin bir parçası olan glomerüler endotelyal glikokaliksin varlığı makromoleküllerin bariyerine anlamlı ölçüde katkı sağlamaktadır. Vasküler endotelyal büyüme faktörü (VEGF) oldukça önemli bir büyüme faktörüdür ve böbrekteki anjiyogenik sitokinleri düzenler. Yapılan çalışmalarda; in vivo modellerde VEGF’ün aşırı ekspresyonunun, in vitro sistemlerde de farmakolojik ajanların dışarıdan verilmesinin fenestraların oluşumları ile yakın birlikteliği gösterilmiştir. Glomerüler endotel hücrelerin, glomerüler fi zyoloji ve patolojisi ile olan beraberliklerinin büyük ölçüde anlaşılması, doğal olarak tedavide muhtemel gelişmelerin olabilirliği sorularını artırmıştır. Örneğin, şiddetli preeklampside böbrek yetmezliği gelişimini önleyeceğinden fenestra formasyonunun artırılması arzu edilir ve yine aynı yolla diyabetik nefropati gibi pek çok tabloda glomerüler fi ltrasyon hızının artırılması sağlanabilir. Yakın gelecekte, glomerüler fi ltrasyon bariyerindeki patolojinin daha iyi anlaşılması için geliştirilen deneysel metodların kullanımı ile birlikte proteinürik böbrek hastalıklarının tedavisinde hedefe yönelik yeni moleküllerin bulunması da söz konusu olacaktır.
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  • 3
220-226
  • Turkish

REFERENCES

References: 

1. Ioannidou S, Deinhardt K, Miotla J, Bradley J, Cheung E,
Samuelsson S, Ng YS, Shima DT: An in vitro assay reveals a role for
the diaphragm protein PV-1 in endothelial fenestra morphogenesis.
Proc Natl Acad Sci 2006; 103(45): 16770-16775
2. Chen S, Kasama Y, Lee JS, Jim B, Marin M, Ziyadeh FN: Podocytederived
vascular endothelial growth factor mediates the stimulation
of alpha3(IV) collagen production by transforming growth factorbeta1
in mouse podocytes. Diabetes 2004; 53(11): 2939-2949
3. Jaimes EA, Hua P, Tian RX, Raij L: Human glomerular
endothelium: Interplay among glucose, free fatty acids angiotensin
II and oxidative stress in hyperglycemia. Am J Physiol Renal
Physiol 2010; 298: 125-132
4. Satchell SC, Braet F: Glomerular endothelial cell fenestrations: An
integral component of the glomerular fi ltration barrier. Am J Physiol
Renal Physiol 2009; 296(5): 947-956
5. Gilbert JS, Verzwyvelt J, Colson D, Arany M, Karumanchi SA,
Granger JP: Recombinant vascular endothelial growth factor 121
infusion lowers blood pressure and improves renal function in rats
with placental ischemia-induced hypertension. Hypertension 2010;
55(2): 380-385
6. Bergmann A, Ahmad S, Cudmore M, Gruber AD, Wittschen P,
Lindenmaier W, Christofori G, Gross V, da Costa Gonzalves AC,
Gröne HJ, Ahmed A, Weich HA: Reduction of circulating soluble
Flt-1 alleviates preeclampsia-like symptoms in a mouse model. J
Cell Mol Med 2010; 14: 1857-1867
7. Satchell SC, Tooke JE: What is the mechanism of microalbuminuria
in diabetes: A role for the glomerular endothelium? Diabetologia
2008; 51(5): 714-725
8. Singh A, Satchell SC, Neal CR, McKenzie EA, Tooke JE, Mathieson
PW: Glomerular endothelial glycocalyx constitutes a barrier to
protein permeability. J Am Soc Nephrol 2007; 18(11): 2885-2893
9. Haraldsson B, Nyström J, Deen WM: Properties of the glomerular
barrier and mechanisms of proteinuria. Physiol Rev 2008; 88(2):
451-487
10. Satchell SC, Braet F: Glomerular endothelial cell fenestrations: An
integral component of the glomerular fi ltration barrier. Am J Physiol
Renal Physiol 2009; 296(5): 947-956
11. Ichimura K, Stan RV, Kurihara H, Sakai T: Glomerular endothelial
cells form diaphragms during development and pathologic
conditions. J Am Soc Nephrol 2008; 19(8): 1463-1471
12. Xu H, Shi BM, Lu XF, Liang F, Jin X, Wu TH, Xu J: Vascular
endothelial growth factor attenuates hepatic sinusoidal
capillarization in thioacetamide-induced cirrhotic rats. World J
Gastroenterol 2008; 14: 2349-2357
13. Harvey SJ, Miner JH: Revisiting the glomerular charge barrier in the
molecular era. Curr Opin Nephrol Hypertens 2008; 17(4): 393-398
14. Ballermann BJ: Contribution of the endothelium to the glomerular
permselectivity barrier in health and disease. Nephron Physiol
2007; 106(2): 19-25
15. Salmon AH, Neal CR, Harper SJ: New aspects of glomerular
fi ltration barrier structure and function: Five layers (at least) not
three. Curr Opin Nephrol Hypertens 2009; 18(3): 197-205
16. Jarad G, Miner JH: Update on the glomerular fi ltration barrier. Curr
Opin Nephrol Hypertens 2009; 18(3): 226-232
17. Levidiotis V, Freeman C, Tikellis C, Cooper ME, Power DA:
Heparanase inhibition reduces proteinuria in a model of accelerated
anti-glomerular basement membrane antibody disease. Nephrology
(Carlton) 2005; 10(2): 167-173
Denizli N ve ark : Glomerüler Endotel
Turk Neph Dial Transpl 2011; 20 (3): 220-226
226
Türk Nefroloji Diyaliz ve Transplantasyon Dergisi
Turkish Nephrology, Dialysis and Transplantation Journal
18. Van den Hoven MJ, Rops AL, Vlodavsky I, Levidiotis V, Berden
JH, van der Vlag J: Heparanase in glomerular diseases. Kidney Int
2007; 72(5): 543-548
19. Levidiotis V, Freeman C, Tikellis C, Cooper ME, Power DA:
Heparanase is involved in the pathogenesis of proteinuria as a result
of glomerulonephritis. J Am Soc Nephrol 2004; 15(1): 68-78
20. Levidiotis V, Kanellis J, Ierino FL, Power DA: Increased expression
of heparanase in puromycin aminonucleoside nephrosis. Kidney Int
2001; 60(4): 1287-1296
21. Jeansson M, Haraldsson B: Morphological and functional evidence for
an important role of the endothelial cell glycocalyx in the glomerular
barrier. Am J Physiol Renal Physiol 2006; 290(1): 111-116
22. Ohlson M, Sorensson J, Haraldsson B: A gel-membrane model of
glomerular charge and size selectivity in series. Am J Physiol Renal
Physiol 2001; 280(3): 396-405
23. Maxhimer JB, Somenek M, Rao G, Pesce CE, Baldwin D Jr,
Gattuso P, Schwartz MM, Lewis EJ, Prinz RA, Xu X: Heparanase-1
gene expression and regulation by high glucose in renal epithelial
cells: A potential role in the pathogenesis of proteinuria in diabetic
patients. Diabetes 2005; 54(7): 2172-2178
24. Holt RC, Webb NJ, Ralph S, Davies J, Short CD, Brenchley PE:
Heparanase activity is dysregulated in children with steroidsensitive
nephrotic syndrome. Kidney Int 2005; 67(1): 122-129
25. Ray PE: Taking a hard look at the pathogenesis of childhood HIVassociated
nephropathy. Pediatr Nephrol 2009; 24(11): 2109-2119
26. Henry CB, Duling BR: TNF-alpha increases entry of
macromolecules into luminal endothelial cell glycocalyx. Am J
Physiol Heart Circ Physiol 2000; 279: 2815-2823
27. Yoshioka T, Ichikawa I, Fogo A: Reactive oxygen metabolites
cause massive, reversible proteinuria and glomerular sieving defect
without apparent ultrastructural abnormality. J Am Soc Nephrol
1991; 2: 902-912
28. Hjalmarsson C, Johansson BR, Haraldsson B: Electron microscopic
evaluation of the endothelial surface layer of glomerular capillaries.
Microvasc Res 2004; 67(1): 9-17
29. Jeansson M, Björck K, Tenstad O, Haraldsson B: Adriamycin alters
glomerular endothelium to induce proteinuria. J Am Soc Nephrol
2009; 20(1): 114-122
30. Ather MH, Masood N, Siddiqui T: Current management of advanced
and metastatic renal cell carcinoma. Urol J 2010; 7(1): 1-9
31. Nagasawa T, Naito T, Matsushita S, Sato H, Katome T, Shiota
H: Effi cacy of intravitreal bevacizumab (Avastin) for short-term
treatment of diabetic macular edema. J Med Invest 2009; 56(3-4):
111-115
32. Sullivan LA, Brekken RA: The VEGF family in cancer and
antibody-based strategies for their inhibition. MAbs 2010; 28: 2 (2):
165-175
33. Eremina V, Baelde HJ, Quaggin SE: Role of the VEGF-a signaling
pathway in the glomerulus: Evidence for crosstalk between
components of the glomerular fi ltration barrier. Nephron Physiol
2007; 106(2): 32-37
34. Datta K, Li J, Karumanchi SA, Wang E, Rondeau E, Mukhopadhyay
D: Regulation of vascular permeability factor/vascular endothelial
growth factor (VPF/VEGF-A) expression in podocytes. Kidney Int
2004; 66 (4): 1471-1478
35. Iliescu R, Fernandez SR, Kelsen S, Maric C, Chade AR: Role
of renal microcirculation in experimental renovascular disease.
Nephrol Dial Transplant 2010; 25(4): 1079-1087
36. Kappers MH, van Esch JH, Sleijfer S, Danser AH, van den Meiracker
AH: Cardiovascular and renal toxicity during angiogenesis
inhibition: Clinical and mechanistic aspects. J Hypertens 2009; 27
(12): 2297-2309
37. Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M,
Weisstuch J, Richardson C, Kopp JB, Kabir MG, Backx PH, Gerber
HP, Ferrara N, Barisoni L, Alpers CE, Quaggin SE: VEGF inhibition
and renal thrombotic microangiopathy. N Engl J Med 2008; 358
(11): 1129-1136
38. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis
S, Sato TN, Yancopoulos GD: Requisite role of angiopoietin-1, a
ligand for the TIE2 receptor, during embryonic angiogenesis. Cell
1996; 87(7): 1171-1180
39. Woolf AS: Angiopoietins: Vascular growth factors looking for roles
in glomeruli. Curr Opin Nephrol Hypertens 2010; 19(1): 20-25
40. Hansen TM, Singh H, Tahir TA, Brindle NP: Effects of
angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are
differentially regulated at the endothelial cell surface Cell Signal
2010; 22 (3): 527-532
41. Milner CS, Hansen TM, Singh H, Brindle NP: Roles of the
receptor tyrosine kinases Tie1 and Tie2 in mediating the effects
of angiopoietin-1 on endothelial permeability and apoptosis.
Microvasc Res 2009; 77(2): 187-191
42. Brindle NP, Saharinen P, Alitalo K: Signaling and functions of
angiopoietin-1 in vascular protection. Circ Res 2006; 98: 1014-1023
43. Salmon AH, Neal CR, Sage LM, Glass CA, Harper SJ, Bates DO:
Angiopoietin-1 alters microvascular permeability coeffi cients in
vivo via modifi cation of endothelial glycocalyx. Cardiovasc Res
2009; 83(1): 24-33

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