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The preventive effect of recombinant human hepatocyte growth factor for hepatic steatosis in a rat model of short bowel syndrome.
J Pediatr Surg. 2022 Jul; 57(7):1286-1292.JP

Abstract

PURPOSE

Short bowel syndrome (SBS) patients require total parenteral nutrition (TPN) following massive small bowel resection (SBR), which may cause intestinal failure-associated liver disease (IFALD), a life-threatening complication. Hepatocyte growth factor (HGF) acts as a potent hepatocyte mitogen with anti inflammatory and antioxidant actions. The present study evaluated the effect of recombinant human HGF (rh-HGF) on SBR and subsequent IFALD using a parentally fed rat model of SBS.

METHODS

Rats underwent jugular vein catheterization for continuous TPN and 90% SBR. They were divided into 2 groups: TPN alone (SBS/TPN group: n = 7) or TPN plus the intravenous administration of rh-HGF (0.3 mg/kg/day) (SBS/TPN+HGF group: n = 7). On day 7, their tissues and stool were harvested to evaluate the effects of HGF.

RESULTS

Regarding the histological findings, based on the nonalcoholic fatty liver disease (NAFLD) activity score, the SBS/TPN+HGF group showed significantly less hepatic steatosis and inflammatory cell infiltration than the SBS/TPN group (NAFLD activity score, 4.00 ± 1.83 vs. 1.00 ± 0.82; p < 0.01). The SBS/TPN+HGF group showed a higher expression of Farnesoid X receptor in the liver and lower expression of Toll-like receptor 4 in the ileum than the SBS/TPN group. Regarding the composition of the bacterial gut microbiota, Actinobacteria, Bacteroidetes and Proteobacteria were decreased in the SBS/TPN+HGF group compared with the SBS/TPN group.

CONCLUSION

In our SBS with TPN rat model, rh-HGF administration had a preventive effect against hepatic steatosis and dysbiosis. rh-HGF may therefore be a potentially effective therapeutic agent for SBS and subsequent IFALD.

TYPE OF STUDY

Experimental research.

Authors+Show Affiliations

Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan; Clinical Training Center, Kagoshima University Hospital, Kagoshima, Japan.Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, School of Medical and Dental Sciences, Kagoshima University Graduate, Kagoshima, Japan.Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, School of Medical and Dental Sciences, Kagoshima University Graduate, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan; Clinical Training Center, Kagoshima University Hospital, Kagoshima, Japan.Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan. Electronic address: sieiri@m.kufm.kagoshima-u.ac.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35396090

Citation

Yano, Keisuke, et al. "The Preventive Effect of Recombinant Human Hepatocyte Growth Factor for Hepatic Steatosis in a Rat Model of Short Bowel Syndrome." Journal of Pediatric Surgery, vol. 57, no. 7, 2022, pp. 1286-1292.
Yano K, Sugita K, Muto M, et al. The preventive effect of recombinant human hepatocyte growth factor for hepatic steatosis in a rat model of short bowel syndrome. J Pediatr Surg. 2022;57(7):1286-1292.
Yano, K., Sugita, K., Muto, M., Matsukubo, M., Onishi, S., Kedoin, C., Matsui, M., Murakami, M., Harumatsu, T., Yamada, K., Yamada, W., Kumagai, K., Ido, A., Kaji, T., & Ieiri, S. (2022). The preventive effect of recombinant human hepatocyte growth factor for hepatic steatosis in a rat model of short bowel syndrome. Journal of Pediatric Surgery, 57(7), 1286-1292. https://doi.org/10.1016/j.jpedsurg.2022.02.030
Yano K, et al. The Preventive Effect of Recombinant Human Hepatocyte Growth Factor for Hepatic Steatosis in a Rat Model of Short Bowel Syndrome. J Pediatr Surg. 2022;57(7):1286-1292. PubMed PMID: 35396090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The preventive effect of recombinant human hepatocyte growth factor for hepatic steatosis in a rat model of short bowel syndrome. AU - Yano,Keisuke, AU - Sugita,Koshiro, AU - Muto,Mitsuru, AU - Matsukubo,Makoto, AU - Onishi,Shun, AU - Kedoin,Chihiro, AU - Matsui,Mayu, AU - Murakami,Masakazu, AU - Harumatsu,Toshio, AU - Yamada,Koji, AU - Yamada,Waka, AU - Kumagai,Kotaro, AU - Ido,Akio, AU - Kaji,Tatsuru, AU - Ieiri,Satoshi, Y1 - 2022/03/13/ PY - 2022/02/06/received PY - 2022/02/23/accepted PY - 2022/4/10/pubmed PY - 2022/6/16/medline PY - 2022/4/9/entrez KW - Farnesoid X receptor KW - Gut micro biota KW - Hepatic steatosis KW - Intestinal failure associated liver disease KW - Short bowel syndrome KW - Toll-like receptor 4 SP - 1286 EP - 1292 JF - Journal of pediatric surgery JO - J Pediatr Surg VL - 57 IS - 7 N2 - PURPOSE: Short bowel syndrome (SBS) patients require total parenteral nutrition (TPN) following massive small bowel resection (SBR), which may cause intestinal failure-associated liver disease (IFALD), a life-threatening complication. Hepatocyte growth factor (HGF) acts as a potent hepatocyte mitogen with anti inflammatory and antioxidant actions. The present study evaluated the effect of recombinant human HGF (rh-HGF) on SBR and subsequent IFALD using a parentally fed rat model of SBS. METHODS: Rats underwent jugular vein catheterization for continuous TPN and 90% SBR. They were divided into 2 groups: TPN alone (SBS/TPN group: n = 7) or TPN plus the intravenous administration of rh-HGF (0.3 mg/kg/day) (SBS/TPN+HGF group: n = 7). On day 7, their tissues and stool were harvested to evaluate the effects of HGF. RESULTS: Regarding the histological findings, based on the nonalcoholic fatty liver disease (NAFLD) activity score, the SBS/TPN+HGF group showed significantly less hepatic steatosis and inflammatory cell infiltration than the SBS/TPN group (NAFLD activity score, 4.00 ± 1.83 vs. 1.00 ± 0.82; p < 0.01). The SBS/TPN+HGF group showed a higher expression of Farnesoid X receptor in the liver and lower expression of Toll-like receptor 4 in the ileum than the SBS/TPN group. Regarding the composition of the bacterial gut microbiota, Actinobacteria, Bacteroidetes and Proteobacteria were decreased in the SBS/TPN+HGF group compared with the SBS/TPN group. CONCLUSION: In our SBS with TPN rat model, rh-HGF administration had a preventive effect against hepatic steatosis and dysbiosis. rh-HGF may therefore be a potentially effective therapeutic agent for SBS and subsequent IFALD. TYPE OF STUDY: Experimental research. SN - 1531-5037 UR - https://www.unboundmedicine.com/medline/citation/35396090/The_preventive_effect_of_recombinant_human_hepatocyte_growth_factor_for_hepatic_steatosis_in_a_rat_model_of_short_bowel_syndrome_ DB - PRIME DP - Unbound Medicine ER -