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LGR5-Expressing Cells in the Healing Process of Post-ESD Ulcers in Gastric Corpus

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Abstract

Background

LGR5 is a promising stem cell marker in gastric pylorus, but there are few reports on its expression in human gastric corpus.

Aims

To investigate the involvement of LGR5 expression in gastric corpus ulcer regeneration in humans.

Methods

LGR5 expression was analyzed in five post-ESD ulcers during the healing process of regenerating epithelial cells of the gastric corpus. LGR5 expression was detected by mRNA in situ hybridization using an RNA scope kit. Immunohistochemistry of MUC6, HIK1083, and pepsinogen 1 (PG1) was performed to identify cell differentiation.

Results

We defined MUC6+/HIK1083−/PG1−, MUC6+/HIK1083+/PG1−, MUC6+/HIK1083+/PG1+, MUC6+/HIK1083−/PG1+, and MUC6-/HIK1083−/PG1+cells as pseudopyloric mucosa (PPM) phase 1 (PPM1), PPM phase 2 (PPM2), PPM phase 3 (PPM3), immature chief cells (ICC), and mature chief cells (MCC) in order from the ulcer center, respectively. In the regenerated mucosa around post-ESD ulcers, LGR5 expression was observed throughout the gland in PPM1–PPM3, but it was limited to the bottom of the gland in ICC and MCC. Furthermore, LGR5 expression was not identified in the normal gastric corpus. The H-score of PPM2 was significantly higher than that of PPM3 (P = 0.0313). The H-score of PPM3 was significantly higher than that of ICC (P = 0.0313). The LGR5 H-score was higher at the immature stage, which decreased gradually with progression of the differentiation stage.

Conclusions

LGR5 expression appears to contribute to mucosal regeneration in the human gastric corpus. The application of LGR5 expression analysis to mucosal regeneration and fundic gland-type gastric tumors is expected.

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Acknowledgments

We are grateful to Masanobu Momose, Yasuyo Shimojo, Naoko Ogiwara, Mieko Horikawa, Akiko Inamura, Chitoshi Arai, Marina Nuno, Kanade Wakabayashi, Naoko Yamaoka, and Tomoya Hachisu at Shinshu University Hospital for their excellent technical assistance. We also thank Mitchell Arico from Edanz Group (https://en-author-services.edanz.com/ac) for editing a draft of this manuscript.

Funding

This study was supported by the Hokuto Foundation for Bioscience (Grant Award to T.U.).

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Authors and Affiliations

  1. Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Yosuke Tobe, Takeshi Uehara, Tomoyuki Nakajima, Mai Iwaya, Yukihiro Kobayashi, Yasuhiro Kinugawa & Hiroyoshi Ota

  2. Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan

    Yasuhiro Kuraishi

  3. Department of Biomedical Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan

    Hiroyoshi Ota

Authors
  1. Yosuke Tobe
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  2. Takeshi Uehara
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  3. Tomoyuki Nakajima
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  4. Mai Iwaya
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  5. Yukihiro Kobayashi
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  6. Yasuhiro Kinugawa
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  7. Yasuhiro Kuraishi
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  8. Hiroyoshi Ota
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Contributions

YT participated in the study design, performed the pathological analysis, and drafted the manuscript. TN, MI, YK, and YK helped with the pathological analysis. TU and YK performed statistical analyses. YT and TN conducted immunohistochemistry. TU and HO revised the draft critically for important intellectual content.

Corresponding author

Correspondence to Takeshi Uehara.

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Tobe, Y., Uehara, T., Nakajima, T. et al. LGR5-Expressing Cells in the Healing Process of Post-ESD Ulcers in Gastric Corpus. Dig Dis Sci 67, 2134–2142 (2022). https://doi.org/10.1007/s10620-021-07059-2

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  • DOI: https://doi.org/10.1007/s10620-021-07059-2

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