Skip to main content

Advertisement

Log in

Involvement of bone marrow-derived endothelial progenitor cells in glomerular capillary repair in habu snake venom-induced glomerulonephritis

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Neovasculogenesis is essential in tissue remodeling. Endothelial progenitor cells (EPCs) mobilize from bone marrow (BM) and participate in neovasculogenesis. This study examined the role of EPCs in a model of reversible glomerulonephritis induced by habu snake venom (HSV). Lethally irradiated FVB/N wild-type mice were transplanted with BM cells from donor transgenic mice expressing β-galactosidase gene under the control of endothelial-specific tie-2 promoter. HSV or saline was injected intravenously after BM transplantation (BMT). The kidneys were removed before injection and at days 1, 7, 28, and 56 after injection. β-Galactosidase-expressing cells were identified by X-gal staining. The expressions of CD31 (endothelial cell marker) and vascular endothelial cell growth factor (VEGF) in renal tissues were examined by immunohistochemistry. In BMT mice injected with saline, few X-gal-positive cells were detected in glomeruli. In HSV-injected mice, X-gal-positive EPCs were increased in damaged glomeruli, reaching maximum at day 28. Recovery of glomeruli was observed at day 56 in association with reduction of X-gal-positive EPCs. VEGF overexpression was detected in glomerular epithelial and endothelial cells, mesangial cells, and EPCs. Our results indicated that EPCs were mobilized into the damaged glomeruli, suggesting EPCs participation in glomerular capillary repair of damaged glomeruli in HSV-induced glomerulonephritis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Abe K, Miyazaki M, Koji T, Furusu A, Ozono Y, Harada T, Sakai H, Nakane PK, Kohno S (1998) Expression of decay accelerating factor mRNA and complement C3 mRNA in human diseased kidney. Kidney Int 54:120–130

    Article  PubMed  CAS  Google Scholar 

  2. Aicher A, Zeiher AM, Dimmeler S (2005) Mobilizing endothelial progenitor cells. Hypertension 45:321–325

    Article  PubMed  CAS  Google Scholar 

  3. Arnold F, West DC (1991) Angiogenesis in wound healing. Pharmacol Ther 52:407–422

    Article  PubMed  CAS  Google Scholar 

  4. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228

    PubMed  CAS  Google Scholar 

  5. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964–3972

    Article  PubMed  CAS  Google Scholar 

  6. Breier G, Damert A, Plate KH, Risau W (1997) Angiogenesis in embryos and ischemic diseases. Thromb Haemost 78:678–683

    PubMed  CAS  Google Scholar 

  7. Cattell V, Bradfield JW (1977) Focal mesangial proliferative glomerulonephritis in the rat caused by habu snake venom. A morphologic study. Am J Pathol 87:511–524

    PubMed  CAS  Google Scholar 

  8. Choi JH, Hur J, Yoon CH, Kim JH, Lee CS, Youn SW, Oh IY, Skurk C, Murohara T, Park YB, Walsh K, Kim HS (2004) Augmentation of therapeutic angiogenesis using genetically modified human endothelial progenitor cells with altered glycogen synthase kinase-3beta activity. J Biol Chem 279:49430–49438

    Article  PubMed  CAS  Google Scholar 

  9. Cornacchia F, Fornoni A, Plati AR, Thomas A, Wang Y, Inverardi L, Striker LJ, Striker GE (2001) Glomerulosclerosis is transmitted by bone marrow-derived mesangial cell progenitors. J Clin Invest 108:1649–1656

    PubMed  CAS  Google Scholar 

  10. D’Amore PA (1986) Growth factors, angiogenesis and metastasis. Prog Clin Biol Res 212:269–285

    PubMed  CAS  Google Scholar 

  11. Folkman J (1985) Tumor angiogenesis. Adv Cancer Res 43:175–203

    Article  PubMed  CAS  Google Scholar 

  12. Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934

    PubMed  CAS  Google Scholar 

  13. Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23:1011–1027

    Article  PubMed  CAS  Google Scholar 

  14. Ikarashi K, Li B, Suwa M, Kawamura K, Morioka T, Yao J, Khan F, Uchiyama M, Oite T (2005) Bone marrow cells contribute to regeneration of damaged glomerular endothelial cells. Kidney Int 67:1925–1933

    Article  PubMed  CAS  Google Scholar 

  15. Ikenaga S, Hamano K, Nishida M, Kobayashi T, Li TS, Kobayashi S, Matsuzaki M, Zempo N, Esato K (2001) Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model. J Surg Res 96:277–283

    Article  PubMed  CAS  Google Scholar 

  16. Imasawa T, Utsunomiya Y, Kawamura T, Zhong Y, Nagasawa R, Okabe M, Maruyama N, Hosoya T, Ohno T (2001) The potential of bone marrow-derived cells to differentiate to glomerular mesangial cells. J Am Soc Nephrol 12:1401–1409

    PubMed  CAS  Google Scholar 

  17. Iruela-Arispe L, Gordon K, Hugo C, Duijvestijn AM, Claffey KP, Reilly M, Couser WG, Alpers CE, Johnson RJ (1995) Participation of glomerular endothelial cells in the capillary repair of glomerulonephritis. Am J Pathol 147:1715–1727

    PubMed  CAS  Google Scholar 

  18. Ito T, Suzuki A, Imai E, Okabe M, Hori M (2001) Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling. J Am Soc Nephrol 12:2625–2635

    PubMed  CAS  Google Scholar 

  19. Jiang M, Wang B, Wang C, He B, Fan H, Guo TB, Shao Q, Gao L, Liu Y (2006) Inhibition of hypoxia-inducible factor-1 alpha and endothelial progenitor cell differentiation by adenoviral transfer of small interfering RNA in vitro. J Vasc Res 43:511–521

    Article  PubMed  CAS  Google Scholar 

  20. Kalka C, Tehrani H, Laudenberg B, Vale PR, Isner JM, Asahara T, Symes JF (2000) VEGF gene transfer mobilizes endothelial progenitor cells in patients with inoperable coronary disease. Ann Thorac Surg 70:829–834

    Article  PubMed  CAS  Google Scholar 

  21. Kawamoto A, Asahara T, Losordo DW (2002) Transplantation of endothelial progenitor cells for therapeutic neovascularization. Cardiovasc Radiat Med 3:221–225

    Article  PubMed  Google Scholar 

  22. Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, Masuda H, Silver M, Ma H, Kearney M, Isner JM, Asahara T (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 103:634–637

    PubMed  CAS  Google Scholar 

  23. Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C, Uchida S, Masuo O, Iwaguro H, Ma H, Hanley A, Silver M, Kearney M, Losordo DW, Isner JM, Asahara T (2003) Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation 107:461–468

    Article  PubMed  Google Scholar 

  24. Kelly DJ, Hepper C, Wu LL, Cox AJ, Gilbert RE (2003) Vascular endothelial growth factor expression and glomerular endothelial cell loss in the remnant kidney model. Nephrol Dial Transplant 18:1286–1292

    Article  PubMed  CAS  Google Scholar 

  25. Kitamura H, Sugisaki Y, Yamanaka N (1995) Endothelial regeneration during the repair process following Habu snake venom-induced glomerular injury. Virchows Arch 427:195–204

    PubMed  CAS  Google Scholar 

  26. Klagsbrun M, D’Amore PA (1991) Regulators of angiogenesis. Annu Rev Physiol 53:217–239

    Article  PubMed  CAS  Google Scholar 

  27. Kong D, Melo LG, Gnecchi M, Zhang L, Mostoslavsky G, Liew CC, Pratt RE, Dzau VJ (2004) Cytokine-induced mobilization of circulating endothelial progenitor cells enhances repair of injured arteries. Circulation 110:2039–2046

    Article  PubMed  CAS  Google Scholar 

  28. Lin F, Mora A, Igarashi P (2005) Intrarenal cells, not bone marrow-derived cells, are the major source for regeneration in postischemic kidney. J Clin Invest 115:1756–1764

    Article  PubMed  CAS  Google Scholar 

  29. Masuda Y, Shimizu A, Mori T, Ishiwata T, Kitamura H, Ohashi R, Ishizaki M, Asano G, Sugisaki Y, Yamanaka N (2001) Vascular endothelial growth factor enhances glomerular capillary repair and accelerates resolution of experimentally induced glomerulonephritis. Am J Pathol 159:599–608

    PubMed  CAS  Google Scholar 

  30. Morita T, Yamamoto T, Churg J (1998) Mesangiolysis: an update. Am J Kidney Dis 31:559–573

    Article  PubMed  CAS  Google Scholar 

  31. Murayama T, Tepper OM, Silver M, Ma H, Losordo DW, Isner JM, Asahara T, Kalka C (2002) Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol 30:967–972

    Article  PubMed  CAS  Google Scholar 

  32. Poulsom R, Forbes SJ, Hodivala-Dilke K, Ryan E, Wyles S, Navaratnarasah S, Jeffery R, Hunt T, Alison M, Cook T, Pusey C, Wright NA (2001) Bone marrow contributes to renal parenchymal turnover and regeneration. J Pathol 195:229–235

    Article  PubMed  CAS  Google Scholar 

  33. Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674

    Article  PubMed  CAS  Google Scholar 

  34. Rookmaaker MB, Smits AM, Tolboom H, Van ‘t Wout K, Martens AC, Goldschmeding R, Joles JA, Van Zonneveld AJ, Grone HJ, Rabelink TJ, Verhaar MC (2003) Bone-marrow-derived cells contribute to glomerular endothelial repair in experimental glomerulonephritis. Am J Pathol 163:553–562

    PubMed  Google Scholar 

  35. Shimizu A, Kitamura H, Masuda Y, Ishizaki M, Sugisaki Y, Yamanaka N (1997) Rare glomerular capillary regeneration and subsequent capillary regression with endothelial cell apoptosis in progressive glomerulonephritis. Am J Pathol 151:1231–1239

    PubMed  CAS  Google Scholar 

  36. Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y, Yamanaka N (1998) Recovery of damaged glomerular capillary network with endothelial cell apoptosis in experimental proliferative glomerulonephritis. Nephron 79:206–214

    Article  PubMed  CAS  Google Scholar 

  37. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T (1999) Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434–438

    Article  PubMed  CAS  Google Scholar 

  38. Urbich C, Aicher A, Heeschen C, Dernbach E, Hormann WK, Zeiher AM Dimmeler S (2005) Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol 39:733–742

    Article  PubMed  CAS  Google Scholar 

  39. Walter DH, Dimmeler S (2002) Endothelial progenitor cells: regulation and contribution to adult neovascularization. Herz 27:579–588

    Article  PubMed  Google Scholar 

  40. Zhang ZG, Zhang L, Jiang Q, Chopp M (2002) Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res 90:284–288

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors thank Ms. Tomomi Kurashige for the excellent technical assistance.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yoko Abe-Yoshio or Katsushige Abe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abe-Yoshio, Y., Abe, K., Miyazaki, M. et al. Involvement of bone marrow-derived endothelial progenitor cells in glomerular capillary repair in habu snake venom-induced glomerulonephritis. Virchows Arch 453, 97–106 (2008). https://doi.org/10.1007/s00428-008-0618-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-008-0618-5

Keywords

Navigation