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Potential mechanisms underlying the effect of hepatocyte growth factor on liver injury in short bowel syndrome model rats

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Abstract

Purpose

The purpose of this study was to investigate the autophagy associated with apoptosis in hepatic damage in the short bowel syndrome rat model.

Methods

SD rats underwent jugular vein catheterization for continuous total parenteral nutrition (TPN) and 90% small bowel resection. Animals were divided into two groups: TPN plus SBS (Control group) or TPN plus SBS plus intravenous administration of HGF (HGF group). On day 7, the rats were harvested, and hepatocellular injury was evaluated.

Results

In an SBS rat model, hepatic steatosis and lobular inflammation were histologically suppressed in the HGF group (p < 0.01). The expression of tumor necrosis factor-α in the HGF group tend to be higher than that in the control group (p = 0.13). The gene expression of transforming Growth Factor-β in the HGF group was suppressed compared to the control group (p < 0.01). HGF treatment may have an antiapoptotic effect via the intrinsic pathway by caspase 9. Protein expressions of Rubicon (p = 0.03) and p62 (p < 0.01) in the HGF group were found to have increased compared to those in the control group.

Conclusion

The inhibitory effect of HGF on hepatic steatosis remains unclear, and further studies focusing on the mechanisms of fat accumulation are needed.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

IFALD:

Intestinal failure-associated liver disease

SBS:

Short bowel syndrome

NAFLD:

Nonalcoholic fatty liver diseases

HGF:

Hepatocyte growth factor

TPN:

Total parenteral nutrition

IL6:

Interleukin-6

TNFα:

Tumor necrosis factor-α

TGFβ:

Transforming growth factor-β

BAX:

Bcl-2-associated X protein

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Acknowledgements

This work was supported by the Laboratory Animal Science Research Support Center Institute for Research Promotion, Kagoshima University. We thank Mr. Brian Quinn for his comments and assistance with this manuscript. We thank Tomomi Kamibayashiyama, a technician at our institution, for her help with the rat’s management, histopathological measurement, biological measurement, western blot, and RT-PCR analyses. We thank Orie Iwaya, a technician at the Department of Pathology, Graduate School of Medical and Dental Science, for her help with histopathological staining. This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS: 23K08031, 22K07848, 22K07894, 22K08719, 22K08736, 22K08757, 21K07867, 21K08623) and a Grant from the Kawano Masanori Memorial Foundation for Promotion of Pediatrics.

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Author notes

  1. Koshiro Sugita and Keisuke Yano contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima City, 890-8520, Japan

    Koshiro Sugita, Keisuke Yano, Yumiko Iwamoto, Masato Ogata, Lynne Takada, Chihiro Kedoin, Masakazu Murakami, Toshio Harumatsu, Shun Onishi, Takafumi Kawano, Mitsuru Muto & Satoshi Ieiri

  2. Department of Pediatric Surgery, Kagoshima City Hospital, Kagoshima, Japan

    Makoto Matsukubo

  3. Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, School of Medical and Dental Sciences, Kagoshima University Graduate, Kagoshima, Japan

    Kotaro Kumagai & Akio Ido

  4. Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan

    Tatsuru Kaji

Authors
  1. Koshiro Sugita
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Contributions

KS, KY, and MM designed the study. KS, KY, SO, and TK performed experiments. YI, MO, and LT supported histopathological assessment. MM, TH, and KS analyzed the data and created the Figure. MM, KK, AI, and TK provided conceptual advice. KS wrote the manuscript in consultation with SI.

Corresponding author

Correspondence to Satoshi Ieiri.

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The authors declare no conflicts of interest in association with the present study.

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Sugita, K., Yano, K., Matsukubo, M. et al. Potential mechanisms underlying the effect of hepatocyte growth factor on liver injury in short bowel syndrome model rats. Pediatr Surg Int 40, 8 (2024). https://doi.org/10.1007/s00383-023-05593-w

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