title: 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.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Tamara
authors.initials: T
authors.lastname: Potikha
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ezra
authors.initials: E
authors.lastname: Ella
authors.affiliation: Laboratory of Immunopathology, Institute of Biology and Experimental Medicine, CONICET, Buenos Aires, Argentina.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Cerliani
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Lina
authors.initials: L
authors.lastname: Mizrahi
authors.affiliation: Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Pappo
authors.affiliation: Laboratory of Immunopathology, Institute of Biology and Experimental Medicine, CONICET, Buenos Aires, Argentina.|Faculty of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Goldenberg
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D037483:Galectin 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006498:Hepatectomy; D006505:Hepatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008115:Liver Regeneration; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D037483:Galectin 1; D051057:Proto-Oncogene Proteins c-akt
keywords: Pathology Section; galectin-1; hepatectomy; lipid metabolism; liver regeneration