Horm Metab Res 2007; 39(12): 862-866
DOI: 10.1055/s-2007-991154
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Clusterin Expression in Porcine Endocrine Cells during Islet Development

M. Schweiger 1 , M. Steffl 1 , W. M. Amselgruber 1
  • 1Institute of Anatomy and Physiology, University of Hohenheim, Stuttgart, Germany
Further Information

Publication History

received 27.11.2006

accepted 10.05.2007

Publication Date:
24 October 2007 (online)

Abstract

Clusterin is a well-known glycoprotein expressed by many cell types involved in multiple physiological functions. In rat pancreatic tissue it is expressed along with islet cell development and found to be involved in regeneration of pancreatic endocrine cells after various types of tissue injuries. These results led us to propose that clusterin might play a crucial role in organization and assembling processes of islet cells during pre- and postnatal development. Therefore, the aim of this study was to find out whether and in which cell type clusterin is expressed during islet cell organization in the porcine species which could play a future role in the field of xenotransplantation. For this purpose we examined the expression pattern of clusterin at different developing stages in the porcine pancreas by double-immunostaining with antibodies against chromogranin A and clusterin, and clarified whether distinct islet hormones were coexpressed with clusterin. Further, we checked by RT-PCR whether clusterin was locally expressed or possibly locally bound to the corresponding receptor. In newborn and up to 3-month-old animals clusterin was found to be expressed in a special cell type which is closely associated and intermingled with other endocrine cells. In fully developed adult islets clusterin-cells then reorganize and were found to be mainly localized in the mantle area of Langerhans islets. Double-immunostaining with antibodies against clusterin and different islet hormones such as insulin, glucagon, and somatostatin clearly demonstrate that clusterin expression was found in an own special cell type and it is also present in a subset of glucagon producing A-cells. Taken together, our results show that clusterin expression in porcine species is found in an own, as yet unidentified cell type during postnatal developmental stages, and probably labels immature precursor cells in adult animals, which finally have the potential to differentiate into glucagon-expressing cells.

References

  • 1 Cirulli V, Baetens D, Rutishauser U, Halban PA, Orci L, Rouiller DG. Expression of neural cell adhesion molecule (N-CAM) in rat islets and its role in islet cell type segregation.  J Cell Sci. 1994;  107 ((Pt 6)) 1429-1436
  • 2 Dahl U, Sjodin A, Semb H. Cadherins regulate aggregation of pancreatic beta-cells in vivo.  Development. 1996;  122 2895-2902
  • 3 Hardikar AA, Marcus-Samuels B, Geras-Raaka E, Raaka BM, Gershengorn MC. Human pancreatic precursor cells secrete FGF2 to stimulate clustering into hormone-expressing islet-like cell aggregates.  Proc Natl Acad Sci USA. 2003;  100 7117-7122
  • 4 Fritz IB, Burdzy K, Setchell B, Blaschuk O. Ram rete testis fluid contains a protein (clusterin) which influences cell-cell interactions in vitro.  Biol Reprod. 1983;  28 1173-1188
  • 5 Thomas-Salgar S, Millis AJ. Clusterin expression in differentiating smooth muscle cells.  J Biol Chem. 1994;  269 17879-17885
  • 6 Silkensen JR, Skubitz KM, Skubitz AP, Chmielewski DH, Manivel JC, Dvergsten JA, Rosenberg ME. Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells.  J Clin Invest. 1995;  96 2646-2653
  • 7 Millis AJ, Luciani M, MacCue HM, Rosenberg ME, Moulson CL. Clusterin regulates vascular smooth muscle cell nodule formation and migration.  J Cell Physiol. 2001;  186 210-219
  • 8 Burkey BF, Stuart WD, Harmony JA. Hepatic apolipoprotein J is secreted as a lipoprotein.  J Lipid Res. 1992;  33 1517-1526
  • 9 Jenne DE, Tschopp J. Clusterin: the intriguing guises of a widely expressed glycoprotein.  Trends Biochem Sci. 1992;  17 154-159
  • 10 Rosenberg ME, Silkensen J. Clusterin: physiologic and pathophysiologic considerations.  Int J Biochem Cell Biol. 1995;  27 633-645
  • 11 Min BH, Jeong SY, Kang SW, Crabo BG, Foster DN, Chun BG, Bendayan M, Park IS. Transient expression of clusterin (sulfated glycoprotein-2) during development of rat pancreas.  J Endocrinol. 1998;  158 43-52
  • 12 Jones SE, Jomary C. Clusterin.  Int J Biochem Cell Biol. 2002;  34 427-431
  • 13 Leskov KS, Klokov DY, Li J, Kinsella TJ, Boothman DA. Synthesis and functional analyses of nuclear clusterin, a cell death protein.  J Biol Chem. 2003;  278 11590-11600
  • 14 Silva HV, Stuart WD, Park YB, Mao SJ, Gil CM, Wetterau JR, Busch SJ, Harmony JA. Purification and characterization of apolipoprotein.  J Biol Chem. 1990;  265 14292-14297
  • 15 Calvo EL, Mallo GV, Fiedler F, Malka D, Vaccaro MI, Keim V, Morisset J, Dagorn JC, Iovanna JL. Clusterin overexpression in rat pancreas during the acute phase of pancreatitis and pancreatic development.  Eur J Biochem. 1998;  254 282-289
  • 16 Redondo M, Villar E, Torres-Munoz J, Tellez T, Morell M, Petito CK. Overexpression of clusterin in human breast carcinoma.  Am J Pathol. 2000;  157 393-399
  • 17 Xie MJ, Motoo Y, Su SB, Sawabu N. Expression of clusterin in pancreatic acinar cell injuries in vivo and in vitro.  Pancreas. 2001;  22 126-134
  • 18 Xie MJ, Motoo Y, Su SB, Mouri H, Ohtsubo K, Matsubara F, Sawabu N. Expression of clusterin in human pancreatic cancer.  Pancreas. 2002;  25 234-238
  • 19 Yang CR, Leskov K, Hosley-Eberlein K, Criswell T, Pink JJ, Kinsella TJ, Boothman DA. Nuclear clusterin/XIP8, an X-ray-induced Ku70-binding protein that signals cell death.  Proc Natl Acad Sci USA. 2000;  97 5907-5912
  • 20 Scaltriti M, Santamaria A, Paciucci R, Bettuzzi S. Intracellular clusterin induces G2-M phase arrest and cell death in PC-3 prostate cancer cells1.  Cancer Res. 2004;  64 6174-6182
  • 21 Park IS, Che YZ, Bendayan M, Kang SW, Min BH. Up-regulation of clusterin (sulfated glycoprotein-2) in pancreatic islet cells upon streptozotocin injection to rats.  J Endocrinol. 1999;  162 57-65
  • 22 Min BH, Kim BM, Lee SH, Kang SW, Bendayan M, Park IS. Clusterin expression in the early process of pancreas regeneration in the pancreatectomized rat.  J Histochem Cytochem. 2003;  51 1355-1365
  • 23 Guesdon JL, Ternynck T, Avrameas S. The use of avidin-biotin interaction in immunoenzymatic techniques.  J Histochem Cytochem. 1979;  27 1131-1139
  • 24 Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures.  J Histochem Cytochem. 1981;  29 577-580
  • 25 Rosenberg ME, Dvergsten J, Correa-Rotter R. Clusterin: an enigmatic protein recruited by diverse stimuli.  J Lab Clin Med. 1993;  121 205-214
  • 26 Harmony JAK. In: Clusterin: role in vertebrate development, function and adaption. New York: Springer-Verlag 1995
  • 27 Portela-Gomes GM, Hacker GW, Weitgasser R. Neuroendocrine cell markers for pancreatic islets and tumors.  Appl Immunohistochem Mol Morphol. 2004;  12 183-192

Correspondence

M. Schweiger

Institute of Anatomy and Physiology

University of Hohenheim

Fruwirthstr. 35

70593 Stuttgart

Germany

Phone: +49/711/4592 24 10

Fax: +49/711/4592 33 08

Email: mschweig@uni-hohenheim.de

    >