Update on the Mechanisms of Liver Regeneration

Abstract

Liver possesses many critical functions such as synthesis, detoxification, and metabolism. It continually receives nutrient-rich blood from gut, which incidentally is also toxin-rich. That may be why liver is uniquely bestowed with a capacity to regenerate. A commonly studied procedure to understand the cellular and molecular basis of liver regeneration is that of surgical resection. Removal of two-thirds of the liver in rodents or patients instigates alterations in hepatic homeostasis, which are sensed by the deficient organ to drive the restoration process. Although the exact mechanisms that initiate regeneration are unknown, alterations in hemodynamics and metabolism have been suspected as important effectors. Key signaling pathways are activated that drive cell proliferation in various hepatic cell types through autocrine and paracrine mechanisms. Once the prehepatectomy mass is regained, the process of regeneration is adequately terminated. This review highlights recent discoveries in the cellular and molecular basis of liver regeneration.

Fig. 1

Cellular circuitry of liver regeneration. A complex crosstalk between various cellular components of liver cells and innate immune cells has been identified during the liver regeneration process. Similarly, evidence of cellular and tissue processes including altered metabolism, hypoxia, gut microbial products, bile acids, and hypoxia have been shown to be major determinants of regenerative response through effect on either hepatocyte directly or through nonparenchymal cells within the liver or cells recruited from the bone marrow. Solid lines represent previously published studies demonstrating a signaling relationship, dotted lines indicate the existence of preliminary evidence. Arrowheads indicate the directionality of cellular signaling and interactions.