The protective effects of hepatocyte growth factor on the intestinal mucosal atrophy induced by total parenteral nutrition in a rat model

Koshiro Sugita,Ayaka Nagano,Satoshi Ieiri,Kotaro Kumagai,Shun Onishi,Mayu Matsui,Makoto Matsukubo,Toshio Harumatsu,Masakazu Murakami,Akio Ido,Mitsuru Muto,Koji Yamada,Tatsuru Kaji,Waka Yamada,Keisuke Yano

doi:10.1007/s00383-021-05002-0

Abstract

PurposeTotal parental nutrition (TPN) causes gastrointestinal mucosal atrophy. The present study investigated the effects of hepatocyte growth factor (HGF) on the intestinal mucosal atrophy induced by TPN.MethodsRats underwent jugular vein catheterization and were divided into four groups: oral feeding (OF), TPN alone (TPN), TPN plus low-dose HGF (0.3 mg/kg/day; TPNLH), and TPN plus high-dose HGF (1.0 mg/kg/day; TPNHH). On day 7, rats were euthanized, and the small intestine was harvested and evaluated histologically. The expression of c-MET, a receptor of HGF, and nutrition transporter protein were evaluated using quantitative polymerase chain reaction.ResultsThe jejunal villus height (VH) and absorptive mucosal surface area in the TPNHH group were significantly higher than in the TPN group (p < 0.05). The VH in the ileum showed the same trend only in the TPNHH group, albeit without statistical significance. The crypt cell proliferation rate (CCPR) of the jejunum in both HGF-treated groups was significantly higher than in the TPN group (p < 0.01). The expression of c-MET and transporter protein in all TPN-treated groups was decreased compared with that in the OF group.ConclusionHGF attenuated TPN-associated intestinal mucosal atrophy by increasing the villus height, which was associated with an increase in CCPR.

Highlights

Parenteral nutrition is a crucial therapeutic modality for various diseases in neonates, children, and adults [1]
The present study investigated the effects of Hepatocyte growth factor (HGF) on total parenteral nutrition (TPN)-associated intestinal mucosal atrophy using a rat model
The major findings in this study were as follows: (1) the jejunal villus height in the HGF-treated groups was significantly greater than that in the TPN group; (2) the absorptive mucosal surface area in the HGFHH group was significantly greater than that in the TPN group; (3) muscular layer in both the jejunum and ileum was in the TPNHH group significantly greater than that in the oral feeding (OF) group; (4) the crypt cell proliferation rate (CCPR) in the TPNLH and TPNHH group was significantly higher than that in the TPN group; and (5) the expression of c-MET and nutrition transporters in the OF group was significantly higher than in the other three groups

Summary

Introduction

Parenteral nutrition is a crucial therapeutic modality for various diseases in neonates, children, and adults [1]. Nutrition therapy for children is essential for life support and growth and development. TPN causes various complications, such as gastrointestinal mucosal atrophy and intestinal failure-associated liver disease (IFALD) [2, 3], including hepatic steatosis, cholestasis, and liver fibrosis [4,5,6]. Our previous study using a TPN rat model or a short bowel syndrome rat model with or without bowel resection showed that both ghrelin [7] and glucagon-like peptide-2 (GLP-2) [8] attenuated intestinal mucosal atrophy and IFALD [9, 10]. The effect of ghrelin on intestinal mucosal atrophy was less marked than that of GLP2, and a high dose of GLP-2 deteriorated the parenteral

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Results

Conclusion