DOI QR코드

DOI QR Code

Extracellular Matrix Metalloproteinase Inducer is Regulated Developmentally and Functionally in the Rat Submandibular Gland

  • Yoo, Hong-Il (Dental Science Research Institute, School of Dentistry, Chonnam National University) ;
  • Suh, Han-Young (Dental Science Research Institute, School of Dentistry, Chonnam National University) ;
  • Kim, Sun-Hun (Dental Science Research Institute, School of Dentistry, Chonnam National University)
  • Received : 2015.08.11
  • Accepted : 2015.09.01
  • Published : 2015.09.30

Abstract

The salivary gland undergoes complex process of growth and differentiation of the branching morphogenesis of ductal system during the prenatal and early postnatal periods which are regulated by various elements in the extracellular matrix. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell adhesion molecule. In the present study, localization and expression of EMMPRIN in development and effects of chorda-lingual denervation and cyclosporine A (CsA) treatment on the EMMPRIN expression were investigated. Immunohistochemistry, RT-PCR and Western blot were used to determine expression level. Immunohistochemistry revealed that EMMPRIN was localized specifically in the cytoplasm of ductal cells, not acini of the submandibular gland all the postnatal periods. At prenatal day 18, when the formation of ducts was not definite, no immunoreactivity was observed. Both Western blot and RT-PCR analyses revealed that EMMPRIN expression was maintained up to postnatal day 7, decreased after postnatal day 10. The EMMPRIN expression was upregulated by the surgical denervation of the chorda-lingual nerve in the gland as well as by the CsA treatment. The present study suggests that EMMPRIN is a crucial molecule for maintaining physiological functions of the salivary gland.

Keywords

References

  1. Denny PC, Ball WD, Redman RS. Salivary glands: a paradigm for diversity of gland development. Crit Rev Oral Biol Med. 1997;8:51-75. https://doi.org/10.1177/10454411970080010301
  2. Gresik EW, Schenkein I, van der Noen H, Barka T. Hormonal regulation of epidermal growth factor and protease in the submandibular gland of the adult mouse. Endocrinology 1981;109:924-929. https://doi.org/10.1210/endo-109-3-924
  3. Chang JC. Canalicular blockage. Aust J Ophthamol. 1973;1:58-62. https://doi.org/10.1111/j.1442-9071.1973.tb01409.x
  4. Gresik EW. Postnatal developmental changes in submandibular glands of rats and mice. J Histochem Cytochem. 1980;28:860-870. https://doi.org/10.1177/28.8.6160181
  5. Yurchenko V, O'Connor M, Dai WW, Guo H, Toole B, Sherry B, Bukrinsky M. CD147 is a signaling receptor for cyclophilin B. Biochem Biophys Res Commun. 2001;288:786-788. https://doi.org/10.1006/bbrc.2001.5847
  6. Igakura T, Kadomatsu K, Kaname T, Muramatsu H, Fan QW, Miyauchi T, Toyama Y, Kuno N, Yuasa S, Takahashi M, Senda T, Taguchi O, Yamamura K, Arimura K, Muramatsu T. A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis. Dev Biol. 1998;194:152-165. https://doi.org/10.1006/dbio.1997.8819
  7. Sun J, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res. 2001;61:2276-2281.
  8. Norgauer J, Hildenbrand T, Idzko M, Panther E, Bandemir E, Hartmann M, Vanscheidt W, Herouy Y. Elevated expression of extracellular matrix metalloproteinase inducer (CD147) and membrane-type matrix metalloproteinases in venous leg ulcers. Br J Dermatol. 2002;147:1180-1186. https://doi.org/10.1046/j.1365-2133.2002.05025.x
  9. Piao S, Zhao S, Guo F, Xue J, Yao G, Wei Z, Huang Q, Sun Y, Zhang B. Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma. J Cancer Res Clin Oncol. 2012;138:627-635. doi: 10.1007/s00432-011-1142-6.
  10. Yang X, Zhang P, Ma Q, Kong L, Li Y, Liu B, Lei D. EMMPRIN contributes to the in vitro invasion of human salivary adenoid cystic carcinoma cells. Oncol Rep. 2012;27:1123-1127. doi: 10.3892/or.2011.1606.
  11. Fernandes RP, Cotanche DA, Lennon-Hopkins K, Erkan F, Menko AS, Kukuruzinska MA. Differential expression of proliferative, cytoskeletal, and adhesive proteins during postnatal development of the hamster submandibular gland. Histochem Cell Biol. 1999;111:153-162. https://doi.org/10.1007/s004180050345
  12. Borghese E. The development in vitro of the submandibular and sublingual glands of Mus musculus. J Anat 1950;84:287-302.
  13. Jacoby F, Leeson CR. The postnatal development of the rat submandibular gland. 14. Laupacis A, Keown PA, Ulan RA, McKenzie N, Stiller CR. Cyclosporin A: a powerful immunosuppressant. Can Med Assoc J. 1982;126:1041-1046.
  14. Yang X, Zhang P, Ma Q, Kong L, Li Y, Liu B, Lei D. EMMPRIN silencing inhibits proliferation and perineural invasion of human salivary adenoid cystic carcinoma cells in vitro and in vivo. Cancer Biol Ther. 2012;13:85-91. https://doi.org/10.4161/cbt.13.2.18455
  15. Piao S, Zhao S, Guo F, Xue J, Yao G, Wei Z, Huang Q, Sun Y, Zhang B. Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma. J Cancer Res Clin Oncol. 2012;138:627-35. https://doi.org/10.1007/s00432-011-1142-6
  16. Fahr A. Cyclosporin clinical pharmacokinetics. Clin Pharmacokinet. 1993;24:472-95. https://doi.org/10.2165/00003088-199324060-00004
  17. Wenger RM. Pharmacology of cyclosporin (sandimmune). II. Chemistry. Pharmacol Rev. 1990;41:243-247.
  18. Galat A. Peptidylproline cis-trans-isomerases: immunophilins. Eur J Biochem. 1993;216:689-707. https://doi.org/10.1111/j.1432-1033.1993.tb18189.x
  19. Yurchenko V, Zybarth G, O'Connor M, Dai WW, Franchin G, Hao T, Guo H, Hung HC, Toole B, Gallay P, Sherry B, Bukrinsky M. Active site residues of cyclophilin A are crucial for its signaling activity via CD147. J Biol Chem. 2002;277:22959-22965. https://doi.org/10.1074/jbc.M201593200
  20. Dardenne M, Savino W, Feutren G, Bach JF. Stimulatory effects of cyclosporin A on human and mouse thymic epithelial cells. Eur J Immunol. 1987;1792:275-279.
  21. Dehpour AR, Nouhnejad P, Mousavizadeh K, Ghfourifar P, Djamali M, Borhanimoghdam B. Cyclosporin A-induced functional and morphological changes in pilocarpine treated rat submandibular glands. Toxicology 1996;108:65-71. https://doi.org/10.1016/S0300-483X(95)03278-N
  22. Malesevic M, Gutknecht D, Prell E, Klein C, Schumann M, Nowak RA, Simon JC, Schiene-Fischer C, Saalbach A. Anti-inflammatory effects of extracellular cyclosporins are exclusively mediated by CD147. J Med Chem. 2013;56:7302-11. https://doi.org/10.1021/jm4007577
  23. Chiu R, Rey O, Zheng JQ, Twiss JL, Song J, Pang S, Yokoyama KK. Effects of altered expression and localization of Cyclophilin A on differentiation of P19 embryonic carcinoma cells. Cell Mol Neurobiol. 2003;23:929-943. https://doi.org/10.1023/B:CEMN.0000005321.11544.cc
  24. Song J, Lu YC, Yokoyama K, Rossi J, Chiu R. Cyclophilin A is required for retinoic acid-induced neuronal differentiation in p19 cells. J Biol Chem. 2004;279:24414-24419. https://doi.org/10.1074/jbc.M311406200
  25. Avramut M, Achim CL. Immunophilins in nervous system degeneration and regeneration. Curr Top Med Chem. 2003;3:1376-1382. https://doi.org/10.2174/1568026033451871
  26. Yang X, Dai J, Li T, Zhang P, Ma Q, Li Y, Zhou J, Lei D. Expression of EMMPRIN in adenoid cystic carcinoma of salivary glands: correlation with tumor progression and patients' prognosis. Oral Oncol. 2010;46:755-760. doi: 10.1016/j.oraloncology.2010.08.008.