Skip to main content
Log in

Effects of high dose retinoic acid on TGF-β2 expression during pancreatic organogenesis

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

Summary

The aim of this study was to investigate the effects of excess all-trans retinoic acid, a vitamin A metabolite, on pancreatic organogenesis and TGF-β2 expression during prenatal development in rats.

First group of animals used as control while a single dose of 60 mg/kg all-trans retinoic acid was ingested by the mothers, at day 8 of gestation (before the neurulation period) in group II and at day 12 of gestation (after the neurulation period) in group III, and all embryos were sacrificed at day 18 of gestation. TGF-β2 expression was detected in the capsule, acini and Langerhans islets in the control group. In the pancreas of group II, dilatation and congestion of interlobular vessels were observed. Langerhans islet structures were completely absent. Moreover acinar TGF-β2 immune reactivity was not determined. In group III, acinar expression of TGF-β2 in acid was similar to that in the controls but their Langerhans islets TGF-β2 immune reactivity was significantly less than the controls.

In view of the present findings we suggest that TGF-β2 plays important role in pancreatic morphogenesis and administration of excess all-trans retinoic acid before neurulation inhibit TGF-β2 expression disrupted pancreatic morphogenesis particularly Langerhans islets. However, its administration after neurulation had less adverse affect on pancreatic organogenesis and TGF-β2 immune reactivity.

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.

Similar content being viewed by others

References

  • Bushan A, Itoh N, Kato S, Thiery JP, Czernichow P, Bellusci S, Scharfmann R (2001) Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis. Development 128(24):5109–5117

    PubMed  Google Scholar 

  • Cabrera-Valladeres G, German MS, Matschinsky FM, Wang J, Fernandez-Mejia C (1999) Effect of retinoic acid on glicokinase activity and gene expression and on insulin secretion in primary cultures of pancreatic islets. Endocrinology 140(7): 3091–3095

    Article  PubMed  Google Scholar 

  • Chen Y, Pan FC, Brandes N, Afelik S, Sölter M, Pieler T. (2004) Retinoic acid signaling is essential for pancreas development and promotes endocrine at the expense of exocrine cell differentiation in Xenopus. Dev Biol 271: 144–160

    Article  PubMed  Google Scholar 

  • Colakoglu N, Kukner A. (2004) Teratogenicity of retinoic acid and its effects on TGF-β2 expression in the developing cerebral cortex of the rat. J Mol Histol 35:823–827

    Article  PubMed  Google Scholar 

  • Crisera CA, Rose MI, Connelly PR, Li M, Colen KL, Longaker MT, Gittes GK. (1999) The Ontogeny of TGF-β1, -β2, -β3, and TGF-β receptor – II expression in the pancreas: Implications for regulation of growth and differentiation. J Pediatr Surg 34(5): 689–694

    Article  PubMed  Google Scholar 

  • Erasmus C, Peny C, Kramer B (2003) Retinoic acid increases the length and volume density of ducts in the rat embryonic pancreas. Dev Growth Differ 45(2):199–207

    Article  PubMed  Google Scholar 

  • Esni F, Stoffers DA, Takeuchi T, Leach SD (2004) Origin of exocrine pancreatic cells from netsin-positive precursors in developing mouse pancreas. Mech Dev 121(1):15–25

    Article  PubMed  Google Scholar 

  • Gittes GK, Galante PE, Hanahan D, Rutter WJ, Debas HT (1996) Lineage-specific morphogenesis in the developing pancreas: Role of mesenchymal factors. Development 122:439–447

    PubMed  Google Scholar 

  • Kim SK, Hebrok M, Melton DA (1997) Notochord to endoderm signaling is required for pancreas development. Development 124: 4243–4252

    PubMed  Google Scholar 

  • Kim SK, Hebrok M (2001) Intercellular signals regulating pancreas development and function. Genes Dev 15(2): 111–127

    Article  PubMed  Google Scholar 

  • Kramer B, Clem P (2003) Regulation of the proportion of insulin cells in embryonic chick pancreas: Effect of a growth factor-reduced extracellular matrix in combination with retinoic acid. In Vitro Cell Dev Biol Anim 39(5–6): 196–198

    Article  PubMed  Google Scholar 

  • Madsen OD, Jensen J, Blume N, Petersen HV, Lund K, Karlsen C, Andersen FG, Jensen PB, Larsson LI, Serup P (1996) Pancreatic development and maturation of the islet B cell. Studies of pluripotent islet cultures. Eur J Biochem 242(3): 435–445

    Article  PubMed  Google Scholar 

  • Martinez A, Cuttitta G, Teitelman G (1998) Expression pattern for adrenomedullin during pancreatic development in the rat reveals a common precursor with other endocrine cell types. Cell Tissue Res 293: 295

    Google Scholar 

  • Miralles F, Battelino T, Czernichow P, Scharfmann R (1998) TGF-beta plays a key role in morphogenesis of the pancreatic islets of Langerhans by controlling the activity of the matrix metalloproteinase MMP-2. J Cell Biol 143(3): 827–836

    Article  PubMed  Google Scholar 

  • Sanvito F, Herrera PL, Huarte J, Nichols A, Montesano R, Orci L, Vassalli JD (1994) TGF-β1 influence the relative development of the exocrine and endocrine pancreas in vitro. Development 120: 3451–3462

    PubMed  Google Scholar 

  • Scharman R (2000) Control of early development of the pancreas in rodents and humans: Implications of signals from the mesenchyme. Diabetologia 43(9): 1083–1092

    Article  PubMed  Google Scholar 

  • Shek FW, Benyon RC, Walker FM, McCrudden PR, Pender SL, Williams EJ, Johnson PA, Johnson CD, Bateman AC, Fine DR, Iradale JP (2002) Expression of transforming growth factor-beta 1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis. Am J Pathol 160(5): 1787–1798

    PubMed  Google Scholar 

  • Skoudy A, Rovira M, Savatier P, Martini F, Leon-Quinto T, Soria B (2004) Transforming growth factor β, fibroblast growth factor and retinoid signaling pathways promote pancreatic exocrine gene expression in mouse embryonic stem cells. Biochem J 379: 749–756

    Article  PubMed  Google Scholar 

  • Stafford D, Prince VE (2002) Retinoic acid signaling is required for a critical early step in zebrafish pancreatic development. Curr Biol 12: 1215–1220

    Google Scholar 

  • Totsuka Y, Tabuchi M, Kojima I, Eto Y, Shibai H, Ogata E (1989) Stimulation of insulin secretion by transforming growth factor-beta. Biochem Biophys Res Commun 158(3): 1060–1065

    Article  PubMed  Google Scholar 

  • Tulachan SS, Doi R, Kawaguchi Y, Tsuji S, Nakajima S, Masui T, Koizumi M, Toyoda E, Mori T, Ito D, Kami K, Fujimoto K, Imamura M (2003) All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal epithelial interactions inembryonic pancreas. Diabetes 52(1): 76–84

    PubMed  Google Scholar 

  • Yamanaka Y, Friess H, Buchler M, Beger HG, Gold LI, Korc M (1993) Synthesis and expression of transforming growth factor beta-1, beta-2, and beta-3 in the endocrine and exocrine pancreas. Diabetes 42(5): 746–756

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Neriman Colakoglu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Colakoglu, N., Kukner, A., Oner, J. et al. Effects of high dose retinoic acid on TGF-β2 expression during pancreatic organogenesis. J Mol Hist 36, 413–418 (2005). https://doi.org/10.1007/s10735-005-9013-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-005-9013-6

Key words

Navigation