Abstract
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.
Similar content being viewed by others
References
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 271:23452–23457
Bagheri N, Chintalacharuvu SR, Emancipator SN (1997) Proinflammatory cytokines regulate FcαR expression by human mesangial cells in vitro. Clin Exp Immunol 107:404–409
Bockholt SM, Burridge K (1993) Cell spreading on extracellular matrix proteins induces tyrosine phosphorylation of tensin. J Biol Chem 268:14565–14567
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 128:1095–1109
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 252:712–715
Fang F, Orend G, Watanabe N, Hunter T, Ruoslahti E (1996) Dependence of cyclin E-CDK2 kinase activity on cell anchorage. Science 271:499–502
Gauer S, Yao J, Schoecklmann HO, Sterzel RB (1997) Adhesion molecules in the glomerular mesangium. Kidney Int 51:1447–1453
Geiger (1999) Vinculin. In: Kreis T, Vale R (eds) Guidebook to the cytoskeletal and motor proteins, 2nd edn. Oxford University Press, Oxford, pp 172–175
Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285:1028–1032
Hartner A, Schöcklmann H, Pröls F, Müller U, Sterzel RB (1999) Alpha8 integrin in glomerular mesangial cells and in experimental glomerulonephritis. Kidney Int 56:1468–1480
Huttenlocher A, Sandborg RR, Horwitz AF (1995) Adhesion in cell migration. Curr Opin Cell Biol 7:697–706
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 103:789–797
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 120:427–431
Kashgarian M, Sterzel RB (1992) The pathobiology of the mesangium. Kidney Int 41:524–529
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 272:717–720
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–F365
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 303:37–45
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 275:1943–1947
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 269:22310–22319
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 125:1067–1075
Lo SH, Weisberg E, Chen LB (1994c) Tensin: a potential link between the cytoskeleton and signal transduction. Bioessays 16:817–823
Lo SH, Yu QC, Degenstein L, Chen LB, Fuchs E (1997) Progressive kidney degeneration in mice lacking tensin. J Cell Biol 136:1349–1361
Pawson T, Gish GD (1992) SH2 and SH3 domains: from structure to function. Cell 71:359–362
Pröls F, Hartner A, Schöcklmann HO, Sterzel RB (1999) Mesangial cells and their adhesive properties. Exp Nephrol 7:137–146
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 11:1149–1155
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 14:1680–1688
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 257:234–238
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 79:21–27
Wilkins JA, Lin S (1986) A re-examination of the interaction of vinculin with actin. J Cell Biol 102:1085–1092
Wilson PD, Burrow CR (1999) Cystic diseases of the kidney: role of adhesion molecules in normal and abnormal tubulogenesis. Exp Nephrol 7:114–124
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yamashita, M., Horikoshi, S., Asanuma, K. et al. Tensin is potentially involved in extracellular matrix production in mesangial cells. Histochem Cell Biol 121, 245–254 (2004). https://doi.org/10.1007/s00418-004-0626-8
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-004-0626-8