Histochemistry and Cell Biology

, Volume 121, Issue 3, pp 245–254 | Cite as

Tensin is potentially involved in extracellular matrix production in mesangial cells

  • Michifumi Yamashita
  • Satoshi Horikoshi
  • Katsuhiko Asanuma
  • Hisatsugu Takahara
  • Isao Shirato
  • Yasuhiko Tomino
Original Paper


Tensin, a focal adhesion protein, is expressed in renal tubular epithelial cells (TECs). Tensin-null mice develop multiple large cysts in the renal proximal tubules. However, the role of tensin in human glomeruli remains unclear. In this study, we assessed tensin localization in human kidney and interaction between tensin and other adhesion components. In human mesangial cells (MCs) and TECs, we confirmed mRNA and protein expressions of tensin by RT-PCR and immunoprecipitation. In normal kidney, immunohistochemistry revealed that tensin was localized in MCs and parietal epithelial cells as well as TECs. In biopsy specimens, the expression of tensin was significantly increased in areas of mesangial expansion in patients with IgA nephropathy and diabetic nephropathy. These results suggest that the expression of tensin is associated with extracellular matrix (ECM) production. In vitro, immunocytochemistry revealed that MCs express tensin mainly at the ends of actin stress fibers and apparently in the focal adhesion areas. Integrin α5, but not α1 and α3, colocalized with tensin. Vinculin and focal adhesion kinase (FAK) were coprecipitated by tensin, suggesting that tensin can mediate signal transduction between cell and ECM through these molecules. Tensin may play important roles in mesangial ECM production through an adhesion complex with integrin α5, FAK, and vinculin.


Focal adhesion Integrin FAK Vinculin 



The authors thank Dr. Yusuke Suzuki for critical reading of the manuscript, Dr. Tsutomu Fujimura for preparation of the illustrations, and Ms Terumi Shibata and Dr. Yukihiko Takeda for technical support. This work was supported, in part, by grants-in-aid for the Special Study Group on Progressive Glomerular Disease from the Ministry of Health, Labor and Welfare of Japan.


  1. Auger KR, Songyang Z, Lo SH, Roberts TM, Chen LB (1996) Platelet-derived growth factor-induced formation of tensin and phosphoinositide 3-kinase complexes. J Biol Chem 271:23452–23457CrossRefPubMedGoogle Scholar
  2. Bagheri N, Chintalacharuvu SR, Emancipator SN (1997) Proinflammatory cytokines regulate FcαR expression by human mesangial cells in vitro. Clin Exp Immunol 107:404–409PubMedGoogle Scholar
  3. Bockholt SM, Burridge K (1993) Cell spreading on extracellular matrix proteins induces tyrosine phosphorylation of tensin. J Biol Chem 268:14565–14567PubMedGoogle Scholar
  4. Chuang JZ, Lin DC, Lin S (1995) Molecular cloning, expression, and mapping of the high affinity actin-capping domain of chicken cardiac tensin. J Cell Biol 128:1095–1109PubMedGoogle Scholar
  5. Davis S, Lu ML, Lo SH, Lin S, Butler JA, Druker BJ, Roberts TM, An Q, Chen LB (1991) Presence of an SH2 domain in the actin-binding protein tensin. Science 252:712–715PubMedGoogle Scholar
  6. Fang F, Orend G, Watanabe N, Hunter T, Ruoslahti E (1996) Dependence of cyclin E-CDK2 kinase activity on cell anchorage. Science 271:499–502PubMedGoogle Scholar
  7. Gauer S, Yao J, Schoecklmann HO, Sterzel RB (1997) Adhesion molecules in the glomerular mesangium. Kidney Int 51:1447–1453PubMedGoogle Scholar
  8. Geiger (1999) Vinculin. In: Kreis T, Vale R (eds) Guidebook to the cytoskeletal and motor proteins, 2nd edn. Oxford University Press, Oxford, pp 172–175Google Scholar
  9. Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285:1028–1032CrossRefPubMedGoogle Scholar
  10. Hartner A, Schöcklmann H, Pröls F, Müller U, Sterzel RB (1999) Alpha8 integrin in glomerular mesangial cells and in experimental glomerulonephritis. Kidney Int 56:1468–1480PubMedGoogle Scholar
  11. Huttenlocher A, Sandborg RR, Horwitz AF (1995) Adhesion in cell migration. Curr Opin Cell Biol 7:697–706CrossRefPubMedGoogle Scholar
  12. Ishida T, Ishida M, Suero J, Takahashi M, Berk BC (1999) Agonist-stimulated cytoskeletal reorganization and signal transduction at focal adhesions in vascular smooth muscle cells require c-Src. J Clin Invest 103:789–797PubMedGoogle Scholar
  13. Jiang B, Yamamura S, Nelson PR, Mureebe L, Kent KC (1996) Differential effects of platelet-derived growth factor isotypes on human smooth muscle cell proliferation and migration are mediated by distinct signaling pathways. Surgery 120:427–431PubMedGoogle Scholar
  14. Kashgarian M, Sterzel RB (1992) The pathobiology of the mesangium. Kidney Int 41:524–529PubMedGoogle Scholar
  15. Katz BZ, Zohar M, Teramoto H, Matsumoto K, Gutkind JS, Lin DC, Lin S, Yamada KM (2000) Tensin can induce JNK and p38 activation. Biochem Biophys Res Commun 272:717–720CrossRefPubMedGoogle Scholar
  16. Kobayashi N, Suzuki Y, Tsuge T, Okumura K, Ra C, Tomino Y (2002) FcRn-mediated transcytosis of immunoglobulin G in human renal proximal tubular epithelial cells. Am J Physiol Renal Physiol 282:F358–F365PubMedGoogle Scholar
  17. Kook S, Kim DH, Shim SR, Kim W, Chun JS, Song WK (2003) Caspase-dependent cleavage of tensin induces disruption of actin cytoskeleton during apoptosis. Biochem Biophys Res Commun 303:37–45CrossRefPubMedGoogle Scholar
  18. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943–1947PubMedGoogle Scholar
  19. Lo SH, An Q, Bao S, Wong WK, Liu Y, Janmey PA, Hartwig JH, Chen LB (1994a) Molecular cloning of chick cardiac muscle tensin. Full-length cDNA sequence, expression, and characterization. J Biol Chem 269:22310–22319PubMedGoogle Scholar
  20. Lo SH, Janmay PA, Hartwig JH, Chen LB (1994b) Interaction of tensin with actin and identification of its three distinct actin-binding domains. J Cell Biol 125:1067–1075PubMedGoogle Scholar
  21. Lo SH, Weisberg E, Chen LB (1994c) Tensin: a potential link between the cytoskeleton and signal transduction. Bioessays 16:817–823PubMedGoogle Scholar
  22. Lo SH, Yu QC, Degenstein L, Chen LB, Fuchs E (1997) Progressive kidney degeneration in mice lacking tensin. J Cell Biol 136:1349–1361CrossRefPubMedGoogle Scholar
  23. Pawson T, Gish GD (1992) SH2 and SH3 domains: from structure to function. Cell 71:359–362PubMedGoogle Scholar
  24. Pröls F, Hartner A, Schöcklmann HO, Sterzel RB (1999) Mesangial cells and their adhesive properties. Exp Nephrol 7:137–146CrossRefPubMedGoogle Scholar
  25. Salgia R, Brunkhorst B, Pisick E, Li JL, Lo SH, Chen LB, Griffin JD (1995) Increased tyrosine phosphorylation of focal adhesion proteins in myeloid cell lines expressing p210BCR/ABL. Oncogene 11:1149–1155PubMedGoogle Scholar
  26. Schaller MD, Hildebrand JD, Shannon JD, Fox JW, Vines RR, Parsons JT (1994) Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol Cell Biol 14:1680–1688PubMedGoogle Scholar
  27. Shikata Y, Shikata K, Matsuda M, Sugimoto H, Wada J, Makino H (1999) Signaling transduction pathway of angiotensin II in human mesangial cells: mediation of focal adhesion and GTPase activating proteins. Biochem Biophys Res Commun 257:234–238CrossRefPubMedGoogle Scholar
  28. Tashiro K, Kodera S, Takahashi Y, Horikoshi S, Shirato I, Tomino Y (1998) Detection of apoptotic cells in glomeruli of patients with IgA nephropathy. Nephron 79:21–27CrossRefPubMedGoogle Scholar
  29. Wilkins JA, Lin S (1986) A re-examination of the interaction of vinculin with actin. J Cell Biol 102:1085–1092PubMedGoogle Scholar
  30. Wilson PD, Burrow CR (1999) Cystic diseases of the kidney: role of adhesion molecules in normal and abnormal tubulogenesis. Exp Nephrol 7:114–124CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Michifumi Yamashita
    • 1
  • Satoshi Horikoshi
    • 1
  • Katsuhiko Asanuma
    • 1
  • Hisatsugu Takahara
    • 1
  • Isao Shirato
    • 1
  • Yasuhiko Tomino
    • 1
  1. 1.Division of Nephrology, Department of Internal MedicineJuntendo University School of MedicineTokyoJapan

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