Galectin-1 is essential for efficient liver regeneration following hepatectomy.

Abstract

Galectin-1 (Gal1) is a known immune/inflammatory regulator which acts both extracellularly and intracellularly, modulating innate and adaptive immune responses. Here, we explored the role of Gal1 in liver regeneration using 70% partial hepatectomy (PHx) of C57BL/6 wild type and Gal1-knockout (Gal1-KO, Lgals1-/-) mice. Gene or protein expression, in liver samples collected at time intervals from 2 to 168 hours post-operation, was tested by either RT-PCR or by immunoblotting and immunohistochemistry, respectively. We demonstrated that Gal1 transcript and protein expression was induced in the liver tissue of wild type mice upon PHx. Liver regeneration following PHx was significantly delayed in the Gal1-KO compared to the control liver. This delay was accompanied by a decreased Akt phosphorylation, and accumulation of the hepatocyte nuclear p21 protein in the Gal1-KO versus control livers at 24 and 48 hours following PHx. Transcripts of several known regulators of inflammation, cell cycle and cell signaling, including some known PHx-induced genes, were aberrantly expressed (mainly down-regulated) in Gal1-KO compared to control livers at 2, 6 and 24 hours post-PHx. Transient steatosis, which is imperative for liver regeneration following PHx, was significantly delayed and decreased in the Gal1-KO compared to the control liver and was accompanied by a significantly decreased expression in the mutant liver of several genes encoding lipid metabolism regulators. Our results demonstrate that Gal1 protein is essential for efficient liver regeneration following PHx through the regulation of liver inflammation, hepatic cell proliferation, and the control of lipid storage in the regenerating liver.

• Authors: Tamara Potikha, Ezra Ella, Juan P Cerliani, Lina Mizrahi, Orit Pappo, Gabriel A Rabinovich, Eithan Galun, Daniel S Goldenberg
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 22 Pg. 31738-54 (May 31 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27166189 (Publication Type: Journal Article)

Chemical References

• Cdkn1a protein, mouse
• Cyclin-Dependent Kinase Inhibitor p21
• Galectin 1
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Cell Cycle
• Cell Proliferation
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Fatty Liver (genetics, metabolism, pathology)
• Galectin 1 (deficiency, genetics, metabolism)
• Genotype
• Hepatectomy
• Hepatitis (genetics, metabolism, pathology)
• Liver (metabolism, pathology, surgery)
• Liver Regeneration
• Mice, Inbred C57BL
• Mice, Knockout
• Phenotype
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Time Factors