All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal/epithelial interactions in embryonic pancreas

Sidhartha Singh Tulachan, Ryuichiro Doi, Yoshiya Kawaguchi, Shoichiro Tsuji, Sanae Nakajima, Toshihiko Masui, Masayuki Koizumi, Eiji Toyoda, Tomohiko Mori, Daisuke Ito, Kazuhiro Kami, Koji Fujimoto, Masayuki Imamura

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Retinoids during the embryonic period act as a mesenchymal inducer in many organs, including kidney, lung, central nervous system, and gut. Retinoic acid (RA) demonstrates insulinotropic effects in adult pancreas, but only a limited study has elucidated its role in pancreatic organogenesis. In this study, we have analyzed the existence of RA-signaling machinery in embryonic pancreas and evaluated its role using in vitro tissue culture experiments. Here we show the presence of endogenous retinaldehyde dehydrogenase 2 (RALDH2), the most effective RA-synthesizing enzyme, RA-binding proteins, and RA receptors (RARs) in embryonic pancreatic tissue. RALDH2 is expressed exclusively in the mesenchyme. Exogenously added all-trans-retinoic acid (atRA) in tissue culture experiments stimulated differentiation of endocrine and duct cells and promoted apoptotic cell death of acinar tissue. Furthermore, we demonstrate that atRA upregulates the PDX-1 expression. Taken together, our data suggest that atRA-mediated mesenchymal/epithelial interactions play an important role in determining the cell fate of epithelial cells via regulation of the PDX-1 gene, leading to the proper formation of the endocrine versus exocrine component during pancreatic organogenesis.

Original languageEnglish
Pages (from-to)76-84
Number of pages9
JournalDiabetes
Volume52
Issue number1
DOIs
Publication statusPublished - 01-01-2003

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Endocrine Cells
Tretinoin
Pancreas
Retinaldehyde
Retinoic Acid Receptors
Organogenesis
Oxidoreductases
Retinoids
Mesoderm
Cell Death
Up-Regulation
Central Nervous System
Epithelial Cells
Kidney
Lung
Enzymes
Genes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Singh Tulachan, Sidhartha ; Doi, Ryuichiro ; Kawaguchi, Yoshiya ; Tsuji, Shoichiro ; Nakajima, Sanae ; Masui, Toshihiko ; Koizumi, Masayuki ; Toyoda, Eiji ; Mori, Tomohiko ; Ito, Daisuke ; Kami, Kazuhiro ; Fujimoto, Koji ; Imamura, Masayuki. / All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal/epithelial interactions in embryonic pancreas. In: Diabetes. 2003 ; Vol. 52, No. 1. pp. 76-84.
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Singh Tulachan, S, 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 in embryonic pancreas', Diabetes, vol. 52, no. 1, pp. 76-84. https://doi.org/10.2337/diabetes.52.1.76

All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal/epithelial interactions in embryonic pancreas. / Singh Tulachan, Sidhartha; Doi, Ryuichiro; Kawaguchi, Yoshiya; Tsuji, Shoichiro; Nakajima, Sanae; Masui, Toshihiko; Koizumi, Masayuki; Toyoda, Eiji; Mori, Tomohiko; Ito, Daisuke; Kami, Kazuhiro; Fujimoto, Koji; Imamura, Masayuki.

In: Diabetes, Vol. 52, No. 1, 01.01.2003, p. 76-84.

Research output: Contribution to journalArticle

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AU - Singh Tulachan, Sidhartha

AU - Doi, Ryuichiro

AU - Kawaguchi, Yoshiya

AU - Tsuji, Shoichiro

AU - Nakajima, Sanae

AU - Masui, Toshihiko

AU - Koizumi, Masayuki

AU - Toyoda, Eiji

AU - Mori, Tomohiko

AU - Ito, Daisuke

AU - Kami, Kazuhiro

AU - Fujimoto, Koji

AU - Imamura, Masayuki

PY - 2003/1/1

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N2 - Retinoids during the embryonic period act as a mesenchymal inducer in many organs, including kidney, lung, central nervous system, and gut. Retinoic acid (RA) demonstrates insulinotropic effects in adult pancreas, but only a limited study has elucidated its role in pancreatic organogenesis. In this study, we have analyzed the existence of RA-signaling machinery in embryonic pancreas and evaluated its role using in vitro tissue culture experiments. Here we show the presence of endogenous retinaldehyde dehydrogenase 2 (RALDH2), the most effective RA-synthesizing enzyme, RA-binding proteins, and RA receptors (RARs) in embryonic pancreatic tissue. RALDH2 is expressed exclusively in the mesenchyme. Exogenously added all-trans-retinoic acid (atRA) in tissue culture experiments stimulated differentiation of endocrine and duct cells and promoted apoptotic cell death of acinar tissue. Furthermore, we demonstrate that atRA upregulates the PDX-1 expression. Taken together, our data suggest that atRA-mediated mesenchymal/epithelial interactions play an important role in determining the cell fate of epithelial cells via regulation of the PDX-1 gene, leading to the proper formation of the endocrine versus exocrine component during pancreatic organogenesis.

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