Skip to main content

Advertisement

Log in

Immunolocalization of FGF-2, -7, -8, -10 and FGFR-1–4 during regeneration of the rat submandibular gland

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in the development of the submandibular gland. Although regeneration of submandibular glands follows a similar process to their development, it is unknown how FGFs and FGFRs are distributed during regeneration of submandibular gland. The aim of this study was to determine the localization of FGFs and FGFRs during such regenerative processes. After 7 days’ obstruction, the submandibular glands were collected at days 0, 1, 3, 7, 11 and 14 after duct release to study regeneration. The regenerative processes of the submandibular gland were investigated by immunohistochemistry for FGF-2, 7, 8, 10 and FGFR-14. Immunohistochemical staining revealed that FGF-2 was moderately expressed in the epithelial cells of duct-like structures (DLS) and newly formed acinar cells (NFAC) at days 0–7, and strongly in intercalated duct (ICD) at control gland and Day 7–14. FGF-7 was localized moderately in NFAC and DLS. FGF-8 was localized moderately in the epithelial cells of DLS during regeneration. Strong positive immunoreactions for FGF-10 were found in NFAC and the epithelial cells of DLS during regeneration, as well as the ICD and lateral surfaces of the maturing acinar cells (MAC). FGFR-1 was expressed moderately in the ICD, and weakly in the NFAC and MAC. Positive immunoreactions for FGFR-2 were not observed during regeneration. Additionally, FGFR-4 was detected strongly in the ICD and slightly in NFAC. These findings suggest that FGF-2, -7, -8 and -10 play important roles in NFAC, MAC, and DLS through FGFR-1 and -4 during regeneration of submandibular gland.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Amano O, Yoshitake Y, Nishikawa K, Iseki S (1993) Basic fibroblast growth factor in rat salivary glands. Cell Tissue Res 273:467–474. doi:10.1007/BF00333701

    Article  CAS  PubMed  Google Scholar 

  • Aure MH, Ruus AK, Galtung HK (2014) Aquaporins in the adult mouse submandibular and sublingual salivary glands. J Mol Histol 45:69–80. doi:10.1007/s10735-013-9526-3

    Article  CAS  PubMed  Google Scholar 

  • Bhaskar SN, Lilly GE, Bhussry B (1966) Regeneration of the salivary glands in the rabbit. J Dent Res 45:37–41. doi:10.1177/0022034566045001260

    Article  CAS  PubMed  Google Scholar 

  • Burgess KL, Dardick I, Cummins MM, Burford-Mason AP, Bassett R, Brown DH (1996) Myoepithelial cells actively proliferate during atrophy of rat parotid gland. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 82:674–680. doi:10.1016/S1079-2104(96)80443-4

    Article  CAS  PubMed  Google Scholar 

  • Celli G, LaRochelle WJ, Mackem S, Sharp R, Merlino G (1998) Soluble dominant-negative receptor uncovers essential roles for fibroblast growth factors in multi-organ induction and patterning. EMBO J 17:1642–1655. doi:10.1093/emboj/17.6.1642

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Colvin JS, Bohne BA, Harding GW, McEwen DG, Ornitz DM (1996) Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. Nature Genet 12:390–397. doi:10.1038/ng0496-390

    Article  CAS  PubMed  Google Scholar 

  • De Moerlooze L, Spencer-Dene B, Revest J-M, Hajihosseini M, Rosewell I, Dickson C (2000) An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development 127:483–492

    PubMed  Google Scholar 

  • Deng CX, Wynshaw-Boris A, Shen MM, Daugherty C, Ornitz DM, Leder P (1994) Murine FGFR-1 is required forearly postimplantation growth and axial organization. Genes Dev 8:3045–3057. doi:10.1101/gad.8.24.3045

    Article  CAS  PubMed  Google Scholar 

  • Deng C, Wynshaw-Boris A, Zhou F, Kuo A, Leder P (1996) Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell 84:911–921. doi:10.1016/S0092-8674(00)81069-7

    Article  CAS  PubMed  Google Scholar 

  • Guo L, Yu Q-C, Fuchs E (1993) Targeting expression of keratinocyte growth factor to keratinocytes elicits striking changes in epithelial differentiation in transgenic mice. EMBO J 12:973–986

    PubMed Central  CAS  PubMed  Google Scholar 

  • Guo L, Degenstein L, Fuchs E (1996) Keratinocyto growth factor is required for hair development but not for wound healing. Genes Dev 10:165–175. doi:10.1101/gad.10.2.165

    Article  CAS  PubMed  Google Scholar 

  • Hamada T, Suda N, Kuroda T (1999) Immunohistochemical localization of fibroblast growth factor receptors in the rat mandibular condylar cartilage and tibial cartilage. J Bone Miner Metab 17:274–282. doi:10.1007/s007740050095

    Article  CAS  PubMed  Google Scholar 

  • Hanks CT, Chaudhry AP (1971) Regeneration of rat submandibular gland following partial extirpation. A light and electron microscopic study. Am J Anat 130:195–207. doi:10.1002/aja.1001300206

    Article  CAS  PubMed  Google Scholar 

  • Hiramatsu Y, Kagami H, Kosaki K, Shigetomi T, Ueda M, Kobayashi S, Sakanaka M (1994) The localization of basic fibroblast growth factor (FGF-2) in rat submandibular glands. Nagoya J Med Sci 57:143–152

    CAS  PubMed  Google Scholar 

  • Hiramatsu Y, Kagami H, Horie K, Okazaki Y, Shigetomi T, Hata K, Kobayashi S, Ueda M (2000) Effects of basic fibroblast growth factor on cultured rat and human submandibular salivary gland cells. Arch Oral Biol 45:593–599. doi:10.1016/S0003-9969(99)00148-x

    Article  CAS  PubMed  Google Scholar 

  • Hoffman MP, Kidder BL, Steinberg ZL, Lakhani S, Ho S, Kleinman HK, Larsen M (2002) Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms. Development 129:5767–5778. doi:10.1242/dev/00172

    Article  CAS  PubMed  Google Scholar 

  • Igarashi M, Finch PW, Aaronson SA (1998) Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7). J Biol Chem 273:13230–13235. doi:10.1074/jbc.273.21.13230

    Article  CAS  PubMed  Google Scholar 

  • Itoh N, Ornitz DM (2004) Evolution of the Fgf and Fgfr gene families. Trends Genet 20:563–569. doi:10.1016/j.tig.2004.08.007

    Article  CAS  PubMed  Google Scholar 

  • Jaskoll T, Zhou YM, Chai Y, Makarenkova HP, Collinson JM, West JD, Hajihosseini MK, Lee J, Melnick M (2002) Embryonic submandibular gland morphogenesis: stage-specific protein localization of FGFs, BMPs, Pax6 and Pax9 in normal mice and abnormal SMG phenotypes in FgfR2-IIIc(+/Delta), BMP(−/−) and Pax6(−/−) mice. Cells Tissues Org 170:83–98. doi:10.1159/000046183

    Article  CAS  Google Scholar 

  • Jaskoll T, Witcher D, Toreno L, Bringas P, Moon AM, Melnick M (2004) FGF8 dose-dependent regulation of embryonic submandibular salivary gland morphogenesis. Dev Biol 268:457–469. doi:10.1016/j.ydbio.2004.01.004

    Article  CAS  PubMed  Google Scholar 

  • Jaskoll T, Abichaker G, Witcher D, Sala FG, Bellusci S, Hajihosseini MK, Melnick M (2005) FGF10/FGFR2b signaling plays essential roles during in vivo embryonic submandibular salivary gland morphogenesis. BMC Dev Biol 5:11. doi:10.1186/1471-213X-5-11

    Article  PubMed Central  PubMed  Google Scholar 

  • Kinkl N, Hageman GS, Sahel JA, Hicks D (2002) Fibroblast growth factor receptor (FGFR) and candidate signaling molecule distribution within rat and human retina. Mol Vis 8:149–160

    PubMed  Google Scholar 

  • Kusafuka K, Tamaguchi A, Kayano T, Takemura T (1998) Immunohistochemical localization of fibroblast growth factors (FGFs) and FGF receptor-1 in human normal salivary glands and pleomorphic adenomas. J Oral Pathol Med 27:287–292. doi:10.1111/j.1600-0714.1998.tb01958.x

    Article  CAS  PubMed  Google Scholar 

  • Li C, Xie X, Wang X, Sun Y, Liu P, Chen L, Qin C (2013) Differential expression and localization of dentin matrix protein 1 (DMP1) fragments in mouse submandibular glands. J Mol Histol 44:231–239. doi:10.1007/s10735-012-9464-5

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • MacArthur CA, Lawshé A, Xu J, Santos-Ocampo S, Heikinheimo M, Chellaiah AT, Ornitz DM (1995) FGF-8 isoforms activate receptor splice forms that are expressed in mesenchymal regions of mouse development. Development 121:3603–3613

    CAS  PubMed  Google Scholar 

  • Madan AK, Kramer B (2005) Immunolocalization of fibroblast growth factor-2 (FGF-2) during embryonic development of the rat submandibular gland. SADJ 58:60–61

    Google Scholar 

  • Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S, Itoh N (2000) FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochem Biophys Res Commun 277:643–649. doi:10.1006/bbrc.2000.3721

    Article  CAS  PubMed  Google Scholar 

  • Okazaki Y, Kagami H, Hattori T, Hishida S, Shigetomi T, Ueda M (2000) Acceleration of rat salivary gland tissue repair by basic fibroblast growth factor. Arch Oral Biol 45:911–919. doi:10.1016/S0003-9969(00)00035-2

    Article  CAS  PubMed  Google Scholar 

  • Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M (1996) Receptor specificity of the fibroblast growth factor family. J Biol Chem 271:15292–15297. doi:10.1074/jbc.271.25.15292

    Article  CAS  PubMed  Google Scholar 

  • Patel VN, Likar KM, Zisman-Rozen S, Cowherd SN, Lassiter KS, Sher I, Yates EA, Turnbull JE, Ron D, Hoffman MP (2008) Specific heparan sulfate structures modulate FGF10-mediated submandibular gland epithelial morphogenesis and differentiation. J Biol Chem 283:9308–9317. doi:10.1074/jbc.M709995200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Powers CJ, McLeskey SW, Wellstein A (2000) Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer 7:165–197. doi:10.1677/erc.0.0070165

    Article  CAS  PubMed  Google Scholar 

  • Qiao J, Uzzo R, Obara-Ishihara T, Degenstein L, Fuchs E, Herzlinger D (1999) FGF-7 modulates ureteric bud growth and nephron number in the developing kidney. Development 126:547–554

    CAS  PubMed  Google Scholar 

  • Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshuzawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S (1999) Fgf10 is essential for limb and lung formation. Nature Genet 21:138–141. doi:10.1038/5096

    Article  CAS  PubMed  Google Scholar 

  • Shimizu O, Shiratsuchi H, Ueda K, Oka S, Yonehara Y (2012) Alteration of the actin cytoskeleton and localization of the α6β1 and α3 integrin during regeneration of the rat submandibular gland. Arch Oral Biol 57:1127–1132. doi:10.1016/j.archoralbio.2012.02.018

    Article  CAS  PubMed  Google Scholar 

  • Steinberg Z, Myers C, Heim VM, Lathrop CA, Rebustini IT, Stewart JS, Larsen M, Hoffman MP (2005) FGFR2b signaling regulates ex vivo submandibular gland epithelial cell proliferation and branching morphogenesis. Development 132:1223–1234. doi:10.1242/dev.01690

    Article  CAS  PubMed  Google Scholar 

  • Takahashi S, Shinzato K, Nakamura S, Domon T, Yamamoto T, Wakita M (2004) Cell death and cell proliferation in the regeneration of atrophied rat submandibular glands after duct ligation. J Oral Pathol Med 33:23–29. doi:10.1111/j.1600-0714.2004.00191

    Article  PubMed  Google Scholar 

  • Ueda K, Shimizu O, Oka S, Saito M, Hide M, Matsumoto M (2009) Distribution of tenascin-C, fibronectin and collagen types III and IV during regeneration of rat submandibular gland. Int J Oral Maxillofac Surg 38:79–84. doi:10.1016/j.ijom.2008.11.004

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Qi S, Wang J, Xia D, Qin L, Zheng Z, Wang L, Zhang C, Jin L, Ding G, Wang S, Fan Z (2014) Spatial and temporal expression of c-Kit in the development of the murine submandibular gland. J Mol Histol 45:381–389. doi:10.1007/s10735-014-9570-7

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Li C, Takahashi K, Slavkin HC, Shum L, Deng C-X (1999) Murine fibroblast growth factor receptor 1a isoforms mediate node regression and are essential for posterior mesoderm development. Dev Biol 208:293–306. doi:10.1006/dbio.1999.9227

    Article  CAS  PubMed  Google Scholar 

  • Yeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, Aaronson SA, Mohammadi M (2003) Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors. Proc Natl Acad Sci USA 100:2266–2271. doi:10.1073/pnas.0436500100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yin SJ, Tang XB, Li FF, Tao Zhang, Yuan ZW, Wang WL, Bai YZ (2013) Spatiotemporal expression of fibroblast growth factor 10 in human hindgut and anorectal development. Cell Tissues Org 198:28–34. doi:10.1159/000351472

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by JSPS KAKENHI Grant No. 24593011 and a Grant from the Dental Research Center and Sato Fund, Nihon University School of Dentistry.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Osamu Shimizu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shimizu, O., Yasumitsu, T., Shiratsuchi, H. et al. Immunolocalization of FGF-2, -7, -8, -10 and FGFR-1–4 during regeneration of the rat submandibular gland. J Mol Hist 46, 421–429 (2015). https://doi.org/10.1007/s10735-015-9631-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-015-9631-6

Keywords

Navigation