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Altered expression of laminin alpha1 in aganglionic colon of endothelin receptor-B null mouse model of Hirschsprung’s disease

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Abstract

Purpose

Laminin, an extracellular matrix molecule, is essential for normal development of the nervous system. The alpha1 subunit of laminin-1 (LAMA1) has been reported to promote neurites and outgrowth and is expressed only during embryogenesis. Previously, we developed a Sox10 transgenic version of the Endothelin receptor-B (Ednrb) mouse to visualize Enteric neural crest-derived cell (ENCC)s with a green fluorescent protein, Venus. We designed this study to investigate the expression of LAMA1 using Sox10-VENUS mice gut.

Methods

We harvested the gut on days 13.5 (E13.5) and 15.5 (E15.5) of gestation. Sox10-VENUS+/Ednrb −/− mice (n = 8) were compared with Sox10-VENUS+/Ednrb +/+ mice (n = 8) as controls. Gene expression of LAMA1 was analysed by real-time RT-PCR. Fluorescent immunohistochemistry was performed to assess protein distribution.

Results

The relative mRNA expression levels of LAMA1 were significantly increased in HD in the proximal and distal colon on E15.5 compared to controls (p < 0.05), whereas there were no significant differences on E13.5. LAMA1 was expressed in the serosa, submucosa and basal lamina in the gut, and was markedly increased in the proximal and distal colon of HD on E15.5.

Conclusions

Altered LAMA1 expression in the aganglionic region may contribute to impaired ENCC migration, resulting in HD. These data could help in understanding the pathophysiologic interactions between LAMA1 and ENCC migration.

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Acknowledgements

The authors thank Dr. Anne-Marie O’Donnell for help in the preparation of the English version of this article and Ms. Mirei Takahashi for assistance the experiments.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Naho Fujiwara, Nana Nakazawa-Tanaka, Katsumi Miyahara & Atsuyuki Yamataka

  2. Department of Pediatric Surgery, Juntendo Nerima Hospital, Tokyo, Japan

    Nana Nakazawa-Tanaka

  3. Research Institute for Disease of Old Age, Juntendo University School of Medicine, Tokyo, Japan

    Eri Arikawa-Hirasawa

  4. Department of Biochemistry and Biophysics, Graduate School of Health Care Science, Tokyo Medical and Dental University, Tokyo, Japan

    Chihiro Akazawa

Authors
  1. Naho Fujiwara
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  2. Nana Nakazawa-Tanaka
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  3. Katsumi Miyahara
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  4. Eri Arikawa-Hirasawa
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  6. Atsuyuki Yamataka
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Corresponding author

Correspondence to Naho Fujiwara.

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Funding

This work was supported by JSPS KAKENHI Grant numbers 15K10929, 16K20347, 17K11521, Takeda Science Foundation and Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics.

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Fujiwara, N., Nakazawa-Tanaka, N., Miyahara, K. et al. Altered expression of laminin alpha1 in aganglionic colon of endothelin receptor-B null mouse model of Hirschsprung’s disease. Pediatr Surg Int 34, 137–141 (2018). https://doi.org/10.1007/s00383-017-4180-6

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  • DOI: https://doi.org/10.1007/s00383-017-4180-6

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