Galectin‑9 ameliorates fulminant liver injury.

Abstract

Fulminant hepatitis is a severe liver disease resulting in hepatocyte necrosis. Galectin‑9 (Gal‑9) is a tandem‑repeat‑type galectin that has been evaluated as a potential therapeutic agent for various diseases that regulate the host immune system. Concanavalin A (ConA) injection into mice results in serious, immune‑mediated liver injury similar to human viral, autoimmune and fulminant hepatitis. The present study investigated the effects of Gal‑9 treatment on fulminant hepatitis in vivo and the effect on the expression of microRNAs (miRNAs), in order to identify specific miRNAs associated with the immune effects of Gal‑9. A ConA‑induced mouse hepatitis model was used to investigate the effects of Gal‑9 treatment on overall survival rates, liver enzymes, histopathology and miRNA expression levels. Histological analyses, TUNEL assay, immunohistochemistry and miRNA expression characterization, were used to investigate the degree of necrosis, fibrosis, apoptosis and infiltration of neutrophils and macrophages. Overall survival rates following ConA administration were significantly higher in Gal‑9‑treated mice compared with control mice treated with ConA + PBS. Histological examination revealed that Gal‑9 attenuated hepatocellular damage, reduced local neutrophil infiltration and prevented the local accumulation of macrophages and liver cell apoptosis in ConA‑treated mice. In addition, various miRNAs induced by Gal‑9 may contribute to its anti‑apoptotic, anti‑inflammatory and pro‑proliferative effects on hepatocytes. The results of the present study demonstrate that Gal‑9 may be a candidate therapeutic target for the treatment of fulminant hepatitis.

• Authors: Tomoko Tadokoro, Asahiro Morishita, Teppei Sakamoto, Shintaro Fujihara, Koji Fujita, Shima Mimura, Kyoko Oura, Takako Nomura, Joji Tani, Hirohito Yoneyama, Hisakazu Iwama, Takashi Himoto, Toshiro Niki, Mitsuomi Hirashima, Tsutomu Masaki
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 16 Issue 1 Pg. 36-42 (Jul 2017) ISSN: 1791-3004 [Electronic] Greece
• PMID: 28534962 (Publication Type: Journal Article)

Chemical References

• Galectins
• MicroRNAs
• galectin 9, mouse
• Concanavalin A

Topics

• Animals
• Apoptosis (drug effects)
• Concanavalin A (adverse effects)
• Disease Models, Animal
• Galectins (administration & dosage, pharmacology)
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Hepatocytes (drug effects, metabolism)
• Liver (drug effects, metabolism, pathology)
• Liver Failure, Acute (drug therapy, etiology, mortality, pathology)
• Liver Function Tests
• Macrophages (drug effects, immunology, metabolism, pathology)
• Male
• Mice
• MicroRNAs (genetics)
• Neutrophil Infiltration (drug effects, immunology)
• Neutrophils (drug effects, immunology, metabolism)
• Survival Rate