Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (PL)

Advances in Clinical and Experimental Medicine

2006, vol. 15, nr 5, September-October, p. 889–895

Publication type: review article

Language: Polish

Rola naczyniowo−śródbłonkowego czynnika wzrostu w patogenezie kłębuszkowych zapaleń nerek

The Role of Vascular Endothelial Growth Factor in Pathogenesis of Glomerulonephritis

Magdalena Makowiecka1,, Danuta Zwolińska1,, Katarzyna Kiliś−Pstrusińska1,

1 Katedra i Klinika Nefrologii Pediatrycznej AM we Wrocławiu

Streszczenie

Naczyniowo−śródbłonkowy czynnik wzrostu (VEGF) jest cytokiną znacznie zwiększającą przepuszczalność naczyń (około 50 000 razy bardziej niż histamina) oraz wykazującą znaczną aktywność proangiogenną. VEGF jest wytwarzany m.in. przez limfocyty T, makrofagi i aktywowane płytki krwi. Zarówno w rozwijającej się, jak i dojrzałej nerce stwierdzono obecność VEGF i jego receptorów VEGFR1 i VEGFR2. Ekspresja VEGF w nerce odbywa się w komórkach nabłonka kanalików dystalnych i zbiorczych oraz podocytach, komórki śródbłonkowe kłębuszka zaś posiadają receptory VEGFR1 i VEGFR2. Zmiany w ekspresji VEGF w nerce stwierdzono w różnych stanach chorobowych (m.in. submikroskopowym kłębuszkowym zapaleniu nerek, nefropatii IgA, nefropatii cukrzycowej). Pomimo licznych badań, nadal jest wiele niejasności co do fizjologicznej roli VEGF i jego udziału w patogenezie kłębuszkowych zapaleń nerek.

Abstract

Vascular endothelial growth factor (VEGF) is a molecule that strongly increases vascular permeability (50 000 times greater than histamine) and stimulates angiogenesis. VEGF is produced, among others, by lymphocytes T, macrophages and activated platelets. VEGF and their receptors (VEGFR1, VEGFR2) were detected both in embryonic and in adult kidney. In the kidney, VEGF is expressed by the podocytes and tubular epithelial cells, while glomerular endothelial cells express VEGFR1 and VEGFR2. Alterations in VEGF expression in the kidney were detected in many diseases (diabetic nephropathy, minimal change disease, IgA nephropathy). Despite of many studies the role of this cytokin in normal renal physiology and in pathogenesis of glomerulonephritis is essentialy unknown.

Słowa kluczowe

VEGF, VEGFR1, VEGFR2, kłębuszkowe zapalenie nerek

Key words

VEGF, VEGFR1, VEGFR2, glomerulonephritis

References (40)

  1. Garin EH: Circulating mediators of proteinuria in idiopathic minimal lesion nephrotic syndrome. Pediatr Nephrol 2000, 14 (8–9), 872–878.
  2. Gandini E, Allaria P, Castiglioni A, d’Amato J, Schiaffino E, Giangrande A: Minimal change nephrotic syndrome with cecum adenocarcinoma. Clin Nephrol 1996, 45, 268–270.
  3. Ferrara N, Gerber HP, LeCouter J: The biology of VEGF and its receptors. Nat Med 2003, 9, 669–676.
  4. Robinson CJ, Stringer SE: The splice variants of vascular growth factor (VEGF) and their receptors. J Cell Sci 2001, 114, 853–865.
  5. Ferrara N: Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004, 25(4), 581–611.
  6. Matsumoto K, Kanmatsuse K: Transforming growth factor−1 inhibits vascular permeability release by T−cells in normal subjects and in patients with minimal change nephritic syndrome. Nephron 2001, 87, 111–117.
  7. Wei MH, Popescu NC, Lerman MI, Merril MJ, Zimonijc DB: Localization of human vascular endothelial growth factor gene, VEGF, at Chromosome 6p12. Human Genetics 1996, 97 (6) 794–797.
  8. Zachary I: Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor. Am J Physiol Cell Physiol 2001, 280, C1375–C1386.
  9. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M: Neuropilin−1 is expressed by endothelial and tumor cells as an isoform−specific receptor for vascular endothelial growth factor. Cell 1998, 92, 735–745.
  10. Bates DO, Harper SJ: Regulation of vascular permeability by vascular endothelial growth factors. Vasc Pharmacol 2003, 39, 225–237.
  11. Zachary I, Gliki G: Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res 2001, 49, 568–581.
  12. Chandra A, Angle N: Vascular endothelial growth factor stimulates a novel calcium−signaling pathway in vascular smooth muscle cells. Surgery 2005, 138, 780–787.
  13. Ferrara N: Vascular endothelial growth factor. Eur J Cancer 1996, 32A, 2413–2422.
  14. Carmeliet P, Ferreira V, Breier G, Polleferyt S, Kieckers L, Gertenstein M, Fahring M, Vandenhoeck A, Eberhardt C, Declerq C, Pawling J, Moons L, Collen D, Nagy A: Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996, 380, 435–439.
  15. Robert B, Abrahamson DR: Control of glomerular capillary development by growth factor/receptor kinases. Pediatr Nephrol 2001, 16, 294–301.
  16. Kitamoto Y, Tokunaga H, Miyamoto K, Tomita K: VEGF is essential molecule for glomerular structuring. Nephrol Dial Transplant 2002, 17 (Suppl. 9), 25–27.
  17. Schrijvers BF, Flyvbjerg A, De Vriese AS: The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 2004, 65, 2003–2017.
  18. Foster RR, Hole R, Anderson K, Satchell SC, Coward PJ, Mathiesos PW, Gillatt DA, Bates DO, Harper SJ: Functional evidence that vascular endothelial growth factor may act as an autocrine factor on human podpcytes. Am J Physiol Renal Physiol 2003, 284, F1263–F1273.
  19. Bates DO, Curry FE: Vascular endothelial growth factor increases hydraulic conductivity of isolated perfused microvassels. Am J Physiol Heart Circ Physiol 1996, 271, H2520–H2528.
  20. Fu BM, Shen S: Structural mechanisms of acute VEGF effect on microvessel permeability Am J Physiol Heart Circ Physiol 2003, 284, H2124–H2135
  21. Wu HM Huang Q, Yuan Y, Granger HJ: VEGF induces NO−dependent hyperpermeability in coronary venules. Am J Physiol Heart Circ Physiol 1996, 271, H2735–H2739.
  22. Murohara T, Horovitz JR, Silver M, Tsurumi Y, Chen D, Sullivan A, Isner IM: Vascular endothelial growth factor/ vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin. Circulation 1998, 97, 99–107.
  23. Kang DH, Hughes J, Mazzali M, Schreiner GF, Johnson RI: Impaired angiogenesis in the remnant kidney model: II. Vascular endothelial growth factor administration reduces renal fibrosis and stabilizes renal function. J Am Soc Nephrol 2001, 12, 1448–1457.
  24. Roberts WG, Palade GE: Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 1995, 108, 2369–2379.
  25. Neal CR, Michel CC: Vascular endothelial frowth factor (VEGF) increases permeability by inducing openings through endothelial cells. Int J Microcirc Clin Exp 1997, 17, 198.
  26. Cooper ME, Vranes D, Youssef S, Stacker SA, Cox AJ, Rizkalla B, Casley DJ, Bach LA, Kelly DJ, Gilbert RE: Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR2 in experimental diabetes. Diabetes 1999, 48, 2229–2239.
  27. Shulman K, Rosen S, Tognazzi K, Manseau EJ, Brown LF: Expression of vascular endothelial growth factor (VPF/VEGF) is altered in many glomerular diseases. J Am Soc Nephrol 1996, 7, 661–666.
  28. Nitta K, Uchida K, Kimata N, Honda K, Horita S, Hayashi T, Ishizuka T, Kobayashi H: Increased serum levels of VEGF in human crescentic glomerulonephritis. Clin Nephrol 1999, 52 (2), 76–82.
  29. Honkanen EO, Teppo AM, Gronhagen−Riska C: Decreased urinary excretion of vascular endothelial growth factor in idiopathic membranous glomerulonephritis. Kidney Int 2000, 57, 2343–2349.
  30. Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, Gerber H−P, Kikkawa Y, Miner JH, Quaggin SE: Glomerular−specific alterations of VEGF−A expression lead to distinct congenital and acquired renal diseases. J Clin Invest 2003, 111, 707–716.
  31. Matsumoto K, Kanmatsuse K: Elevated VEGF levels in urine of patients with minimal−change nephrotic syndrome. Clin Nephrol 2001, 55 (4), 269–274.
  32. Webb NJ, Watson CJ, Roberts IS, Bottomley MJ, Jones CA, Lewis MA, Postlethwaite RJ, Brenchley PE: Circulating VEGF is not increased during relapses of steroid−sensitive nephrotic syndrome. Kidney Int 1999, 55 (3), 1063–1071.
  33. Webb NJ, Bottomley MJ, Watson CJ, Brenchley PE: Vascular endothelial growth factor (VEGF) is released from platelets during blood clotting: implications for measurements of circulating VEGF levels in clinical disease. Clin Sci (Lond) 1998, 94 (4), 395–404.
  34. Bailey E, Bottomley MJ, Westwell S, Pringle JH, Furness PN, Feehally J, Brenchley PEC, Harper SJ: Vascular endothelial growth factor mRNA expression in minimal change, membranous, and diabetic nephropathy demonstrated by on−isotopic in situ hybridisation. J Clin Pathol 1999, 52 (10), 735–738.
  35. Boner G, Cox AJ, Kelly DJ, Tobar A, Berheim J, Langham RG, Cooper ME, Gilbert RE: Does vascular endothelial growth factor (VEGF) play a role in the pathogenesis of minimal change disease? Nephrol Dial Transplant 2003, 18, 2293–2299.
  36. Holt RCL, Ralph SA, Webb NJA, Watson CJ, Clark AGB, Mathieson PW, Brenchley PEC: Steroid−sensitive nephrotic syndrome and vascular endothelial growth factor gene polimorfisms. Eur J Immunogen 2003, 30, 1–3.
  37. Ostendorf T, Kunter U, Eitner F, Loos A, Regele H, Kerjaschki D, Henninger DD, Janjic N, Floege J: VEGF 165 mediates glomerular endothelial repair. J Clin Invest 1999, 104, 913–923.
  38. Kim YG, Suga S, Kang DH, Jefferson JA, Mazzali M, Gordon KL, Matusi K, Breiteneder−Geleff S, Shankland SJ, Huges J, Kerjaschki D, Schreiner GF, Johnson RJ: Vascular endothelial growth factor accelerates renal recovery in experimental thrombotic microangiopathy. Kidney Int 2000, 58, 2390–2399.
  39. Sugimoto H, Hamano Y, Charytan D, Cosgrove D, Kieran M, Sudhakar A, Kalluri R: Neutralization of circulating vascular endothelial growth factor (VEGF) by anti−VEGF antibodies and soluble VEGF receptor 1 (sFlt−1) induces proteinuria. J Biol Chem 2003, 278, 12605–12608.
  40. Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, Griffing S, Bergsland E: Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003, 21, 60–65.
© Wroclaw Medical University