Potikha Tamara, Ella Ezra, Cerliani Juan P, Mizrahi Lina, Pappo Orit, Rabinovich Gabriel A, Galun Eithan, Goldenberg Daniel S
The Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Laboratory of Immunopathology, Institute of Biology and Experimental Medicine, CONICET, Buenos Aires, Argentina.
Oncotarget. 2016 May 31;7(22):31738-54. doi: 10.18632/oncotarget.9194.
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.
半乳糖凝集素-1（Gal1）是一种已知的免疫/炎症调节因子，可在细胞外和细胞内发挥作用，调节先天性和适应性免疫反应。在此，我们利用C57BL/6野生型和Gal1基因敲除（Gal1-KO，Lgals1-/-）小鼠进行70%部分肝切除术（PHx），探讨了Gal1在肝脏再生中的作用。分别通过RT-PCR或免疫印迹及免疫组织化学检测术后2至168小时不同时间点采集的肝脏样本中的基因或蛋白表达。我们证明，PHx后野生型小鼠肝脏组织中Gal1转录本和蛋白表达被诱导。与对照肝脏相比，Gal1-KO小鼠PHx后的肝脏再生明显延迟。这种延迟伴随着Akt磷酸化的降低，以及在PHx后24和48小时，Gal1-KO肝脏与对照肝脏相比，肝细胞核p21蛋白的积累。与对照肝脏相比，在PHx后2、6和24小时，Gal1-KO中几种已知的炎症、细胞周期和细胞信号调节因子的转录本，包括一些已知的PHx诱导基因，表达异常（主要下调）。PHx后肝脏再生所必需的短暂性脂肪变性在Gal1-KO中与对照肝脏相比明显延迟且减少，并伴随着突变肝脏中几种编码脂质代谢调节因子的基因表达显著降低。我们的结果表明，Gal1蛋白通过调节肝脏炎症、肝细胞增殖以及控制再生肝脏中的脂质储存，对PHx后高效的肝脏再生至关重要。
