Skip to main content

Advertisement

SpringerLink
Log in

Immunohistochemical study on caveolin-1α in regenerating process of tubular cells in gentamicin-induced acute tubular injury in rats

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

Abstract

Caveolin-1, a principal component of caveolae, modulates growth signaling, endocytosis, and intracellular transport. We examined the expression of caveolin-1α and its relation to cell cycle and caveolin-interacting growth factor receptors in regenerating proximal tubules (PTs) after gentamicin-induced acute renal failure in rats. Caveolin-1α appeared in regenerating PTs as early as day 4 after last gentamicin, peaked at days 6 to 8, and showed cytoplasmic pattern after day 8. Immunoelectron microscopy revealed caveolin-1α-positive caveolae on the cell membrane and in cytoplasms in regenerating PTs at days 4 to 8 and caveolin-positivity confined to cytoplasms after day 10. The number of PT cells with proliferation markers peaked at day 6 and decreased afterwards as expression of cyclin-dependent kinase inhibitors increased. Platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) were colocalized with caveolin-1α in proliferating PTs as early as day 4. Phosphorylated EGFR increased at day 8 and afterwards when caveolins dissociated from EGFR or decreased. In case of PDGFR-β, phosphorylation seemed to be associated with the increase and association of caveolins to the receptors. Our results suggest that transient expression of caveolin-1α in early regenerating PTs might contribute to the regenerating process of PTs through modulating growth factor receptors.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Breton S, Lisanti MP, Tyszkowski R, McLaughlin M, Brown D (1998) Basolateral distribution of caveolin-1 in the kidney. Absence from H+-atpase-coated endocytic vesicles in intercalated cells. J Histochem Cytochem 46:205–214

    PubMed  CAS  Google Scholar 

  2. Couet J, Sargiacomo M, Lisanti MP (1997) Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem 272:30429–30438

    Article  PubMed  CAS  Google Scholar 

  3. Fujita Y, Maruyama S, Kogo H, Matsuo S, Fujimoto T (2004) Caveolin-1 in mesangial cells suppresses MAP kinase activation and cell proliferation induced by bFGF and PDGF. Kidney Int 66:1794–1804

    Article  PubMed  CAS  Google Scholar 

  4. Galbiati F, Volonte D, Liu J, Capozza F, Frank PG, Zhu L, Pestell RG, Lisanti MP (2001) Caveolin-1 expression negatively regulates cell cycle progression by inducing G0/G1 arrest via p53/p21WAF1/Cip1-dependent mechanism. Mol Biol Cell 12:2229–2244

    PubMed  CAS  Google Scholar 

  5. Goto T, Fujigaki Y, Sun DF, Yamamoto T, Hishida A (2004) Plasma protein extravasation and vascular endothelial growth factor expression with endothelial nitric oxide synthase induction in gentamicin-induced acute renal failure in rats. Virchows Arch 444:362–374

    Article  PubMed  CAS  Google Scholar 

  6. Harris RC (1997) Growth factors and cytokines in acute renal failure. Adv Renal Replace Ther 4:43–53

    CAS  Google Scholar 

  7. Lan HY, Mu W, Nikolic-Paterson DJ, Atkins RC (1995) A novel, simple, reliable, and sensitive method for multiple immunoenzyme staining: use of microwave oven heating to block antibody crossreactivity and retrieve antigens. J Histochem Cytochem 43:97–102

    PubMed  CAS  Google Scholar 

  8. Liu P, Ying Y, Anderson RG (1997) Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae. Proc Natl Acad Sci USA 94:13666–13670

    Article  PubMed  CAS  Google Scholar 

  9. Liu P, Rudick M, Anderson RG (2002) Multiple functions of caveolin-1. J Biol Chem 277:41295–41298

    Article  PubMed  CAS  Google Scholar 

  10. Mahmoudi M, Willgoss D, Cuttle L, Yang T, Pat B, Winterford C, Endre Z, Johnson DW, Gobe GC (2003) In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure. J Pathol 200:396–405

    Article  PubMed  CAS  Google Scholar 

  11. Marti U, Hug M (1995) Acinar and cellular distribution and mRNA expression of the epidermal growth factor receptor are changed during liver regeneration. J Hepatol 23:318–327

    PubMed  CAS  Google Scholar 

  12. Matveev SV, Smart EJ (2002) Heterologous desensitization of EGF receptors and PDGF receptors by sequestration in caveolae. Am J Physiol Cell Physiol 282:C935–C946

    PubMed  CAS  Google Scholar 

  13. Mendez AJ, Lin G, wade DP, Lawn RM, Oram JF (2001) Membrane lipid domains distinct from cholesterol/sphingomyelin rich rafts are involved in the ABCA-1-mediated lipid secretory pathway. J Biol Chem 276:3158–3166

    Article  PubMed  CAS  Google Scholar 

  14. Mineo C, James GL, Smart EJ, Anderson RG (1996) Localization of epidermal growth factor-stimulated Ras/Raf-1 interaction to caveolae membrane. J Biol Chem 271:11930–11935

    Article  PubMed  CAS  Google Scholar 

  15. Morin NJ, Laurent G, Nonclercq D, Toubeau G, Heuson-Stiennon JA, Bergeron MG, Beauchamp D (1992) Epidermal growth factor accelerates renal tissue repair in a model of gentamicin nephrotoxicity in rats. Am J Physiol 263:F806–F811

    PubMed  CAS  Google Scholar 

  16. Nakagawa T, Sasahara M, Haneda M, Kataoka H, Nakagawa H, Yagi M, Kikkawa R, Hazama F (1999) Role of PDGF B-chain and PDGF receptors in rat tubular regeneration after acute injury. Am J Pathol 155:1689–1699

    PubMed  CAS  Google Scholar 

  17. Nichols B (2003) Caveosomes and endocytosis of lipid rafts. J Cell Sci 116:4707–4714

    Article  PubMed  CAS  Google Scholar 

  18. Nouwen EJ, Verstrepen WA, Buyssens N, Zhu MQ, De Broe ME (1994) Hyperplasia, hypertrophy, and phenotypic alterations in the distal nephron after acute proximal tubular injury in the rat. Lab Invest 70:479–493

    PubMed  CAS  Google Scholar 

  19. Parolini I, Sargiacomo M, Galbiati F, Rizzo G, Grignani F, Engelman JA, Okamoto T, Ikezu T, Scherer PE, Mora R, Rodriguez-Boulan E, Peschle C, Lisanti MP. (1999) Expression of caveolin-1 is required for the transport of caveolin-2 to the plasma membrane. Retention of caveolin-2 at the level of the Golgi complex. J Biol Chem 274:25718–25725

    Article  PubMed  CAS  Google Scholar 

  20. Razani B, Woodman SE, Lisanti MP (2002) Caveolae: from cell biology to animal physiology. Pharmacol Rev 54:431–467

    Article  PubMed  CAS  Google Scholar 

  21. Vogel U, Sandvig K, van Deurs B (1998) Expression of caveolin-1 and polarized formation of invaginated caveolae in Caco-2 and MDCK II cells. J Cell Sci 111:825–832

    PubMed  CAS  Google Scholar 

  22. Volonte D, Galbiati F, Lisanti MP (1999) Visualization of caveolin-1, a caveolar marker protein, in living cells using green fluorescent protein (GFP) chimeras. The subcellular distribution of caveolin-1 is modulated by cell-cell contact. FEBS Lett 445:431–439

    Article  PubMed  CAS  Google Scholar 

  23. Yamamoto M, Toya Y, Jensen RA, Ishikawa Y (1999) Caveolin is an inhibitor of platelet-derived growth factor receptor signaling. Exp Cell Res 247:380–388

    Article  PubMed  CAS  Google Scholar 

  24. Zager RA, Johnson A, Hanson S, dela Rosa V (2002) Altered cholesterol localization and caveolin expression during the evolution of acute renal failure. Kidney Int 61:1674–1683

    Article  PubMed  CAS  Google Scholar 

  25. Zhou H, Kato A, Yasuda H, Miyaji T, Fujigaki Y, Yamamoto T, Yonemura K, Hishida A (2004) The induction of cell cycle regulatory and DNA repair proteins in cisplatin-induced acute renal failure. Toxicol Appl Pharmacol 200:111–120

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We thank Ms. Etsuko Hakamata for the excellent technical assistance. This work was presented in part at the XLIIth Congress of the ERA-EDTA in Istanbul, Turkey, 2005.

Author information

Authors and Affiliations

  1. First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192, Hamamatsu, Japan

    Yoshihide Fujigaki, Masanori Sakakima, Yuan Sun, Tetsuo Goto, Naro Ohashi, Hirotaka Fukasawa, Takayuki Tsuji, Tatsuo Yamamoto & Akira Hishida

Authors
  1. Yoshihide Fujigaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masanori Sakakima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tetsuo Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naro Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hirotaka Fukasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takayuki Tsuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tatsuo Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Akira Hishida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshihide Fujigaki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fujigaki, Y., Sakakima, M., Sun, Y. et al. Immunohistochemical study on caveolin-1α in regenerating process of tubular cells in gentamicin-induced acute tubular injury in rats. Virchows Arch 450, 671–681 (2007). https://doi.org/10.1007/s00428-007-0417-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-007-0417-4

Keywords

Search

Navigation