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The role of hedgehog signaling during gastric regeneration

  • Original Article—Alimentary Tract
  • Published:
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Abstract

Background

Hedgehog signaling plays critical roles during embryonic development. It is also involved in tissue regeneration and carcinogenesis in various adult tissues. Moreover, it regulates the maintenance of cancer stem cells and adult stem cells. Although hedgehog signaling is important in gastric carcinogenesis, its role in gastric regeneration has not been previously examined. In the present study, we evaluated the expression and roles of hedgehog signaling during gastric regeneration.

Methods

Gastric ulcers were induced by serosal application of an acetic acid solution in mice. Sham-operated mice served as controls. The proliferation of gastric progenitor cells was studied using bromodeoxyuridine (BrdU). The expression of hedgehog signaling molecules and the differentiation of gastric progenitor cells were examined by immunohistochemical staining and Western blotting.

Results

One day after the induction of gastric ulcer, the proliferation of gastric progenitor cells increased; however, the expression of hedgehog signaling molecules, including sonic hedgehog (Shh), Indian hedgehog (Ihh), desert hedgehog (Dhh), and patched (Ptch1) decreased at the ulcer margin. From 5 days after the induction of gastric ulcer, newly generated gastric glands and their differentiation were observed at the ulcer margin. The expression of hedgehog signaling molecules gradually increased in the newly generated gastric glands of the ulcer margin. Cyclopamine, a specific inhibitor of hedgehog signaling, significantly inhibited the differentiation of mucous cells and parietal cells during the gastric regeneration process.

Conclusion

The above results suggest that hedgehog signaling is involved in the differentiation of gastric progenitor cells during the gastric ulcer repair process.

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Acknowledgments

This study was supported by a Medical Research Institute Grant (2007-2), Pusan National University, a Korea Research Foundation Grant funded by the Korean government (MOEHRD) (KRF-2006-331-E00057), and the MRC program of MOST/KOSEF (R13-2005-009).

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Authors and Affiliations

  1. Department of Internal Medicine, School of Medicine, Pusan National University, Mulgeum-Eup, Beomeo-Ri, Yangsan, 626-770, South Korea

    Dae-Hwan Kang & Gwang-Ha Kim

  2. Department of Anatomy, School of Medicine, Pusan National University, Mulgeum-Eup, Beomeo-Ri, Yangsan, 626-770, South Korea

    Myoung-Eun Han, Moo-Ho Song, Young-Suk Lee, Eun-Hee Kim, Hyun-Jung Kim, Sik Yoon, Sun-Yong Baek, Bong-Seon Kim, Jae-Bong Kim & Sae-Ock Oh

  3. Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Mulgeum-Eup, Beomeo-Ri, Yangsan, 626-770, South Korea

    Myoung-Eun Han, Sik Yoon & Sae-Ock Oh

  4. Department of Surgery, School of Medicine, Pusan National University, Mulgeum-Eup, Beomeo-Ri, Yangsan, 626-770, South Korea

    Dong-Heon Kim

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  1. Dae-Hwan Kang
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Corresponding author

Correspondence to Sae-Ock Oh.

Additional information

Dae-Hwan Kang, Myoung-Eun Han: these authors contributed equally to this work.

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Kang, DH., Han, ME., Song, MH. et al. The role of hedgehog signaling during gastric regeneration. J Gastroenterol 44, 372–379 (2009). https://doi.org/10.1007/s00535-009-0006-1

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  • DOI: https://doi.org/10.1007/s00535-009-0006-1

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