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.

Lack of galectin‐1 exacerbates chronic hepatitis, liver fibrosis, and carcinogenesis in murine hepatocellular carcinoma model

“…Interestingly, there is still no evidence linking Gal1 and Opn expression. In a previous study exploring the role of Gal1 in liver regeneration (22), we found no differences in Opn expression between Gal1-KO and wild-type mice at 2 and 3 d posthepatectomy (unpublished results). Opn is a multifunctional protein, which occurs in both secreted and intracellular forms and interacts with the immune system and other cell types in the injured liver.…”

“…These results are consistent with the fact that Gal1 is just one of multiple factors dictating the outcome of CLImediated hepatocarcinogenesis. Likewise, loss of Gal1 resulted in only a 1-d retardation of liver regeneration (22).…”

“…Wild-type B6 mice were obtained from Envigo RMS Ltd. (Jerusalem, Israel); the Lgals1-KO mutants of the B6 strain were kindly provided by Prof. Francoise Poirier (Institut Jacques Monod, Universités P6 and P7, Paris, France) and propagated in our facility. The Mdr2-KO/B6 and Gal1-KO/FVB mice were generated in our laboratory (21,22). The dKO/FVB and dKO/B6 strains we generated by mating Gal1-KO with Mdr2-KO mice of either B6 or FVB backgrounds to generate F1 double heterozygous mice.…”

Galectin 1 in dermatology: current knowledge and perspectives

“…The most important biological properties and actions of this galectin include involvement in morphogenesis, angiogenesis, regulation of the cell cycle, proliferation and immune response, cell-cell and cell-matrix adhesion, apoptosis, inflammation, tumor invasion and metastasis (10,11,(15)(16)(17)(18)(19), regulation of the innate and the adaptive immune response (20), promotion of the subsidence of autoimmune inflammation and suppression of allergeninduced inflammation and antibacterial immune response (21), contribution to the induction of B cells' regulatory function (22) and to the escape of tumor cells from immune surveillance (21), involvement in tumoral angiogenesis, hypoxia and metastasis (23), and the mechanisms of microglial modulation, polarization, and remyelination (24).…”

Presence of galectin-1 in the epidermal and dermal thickening of keloid tissues

“…Similarly, recent studies related to Gal-1 expression have shown upregulated levels of Gal-1 and collagen I in lung fibrosis [51]. Nonetheless, we can not exclude the possibility that in keloid tissues Gal-1 might also regulates the dermis inflammation and fibroblasts proliferation; moreover, considering that intracellularly Gal-1 inhibits both the soluble and cellular mediators of the inflammatory response in acute and chronic inflammation [27], and regulates the liver inflammation and hepatic cells proliferation in liver regeneration [58]. Of note, a protective role for Gal-1 during acute myocardial infarction by preventing cardiac inflammation has been proposed [59].…”