Modulation of liver regeneration by the nuclear factor erythroid 2-related factor 2

2023

Advances in Redox Research, Vol 7, Iss , Pp 100066- (2023)

The liver is provided with peculiar regenerative features, initiated by resection or acute/chronic injuries. Preservation of cell phenotype (“phenotypic fidelity”) characterizes liver regeneration triggered by resection and acute damage. On the contrary, this mechanism is defective during chronic liver injury, in which regeneration can be supported by activation of facultative progenitors or trans-differentiation of parenchymal cells.Both resection and acute/chronic damages may alter hepatic redox homeostasis. This modification may impact the regulation of pathways involved in liver regeneration, including proliferation and trans-differentiation of parenchymal cells, as well as activation of facultative progenitors. The regenerative process of the liver may be modulated by several redox-dependent transcription factors. Among them, the nuclear factor erythroid 2-related factor 2 (NRF2) plays a determinant role. After hepatic resection, NRF2 contributes to the regulation of parenchymal proliferation, maintaining newly regenerated hepatocytes completely differentiated. NRF2 deactivation induces oxidative stress-related insulin resistance and impairs regeneration by blocking pro-mitogenic and anti-apoptotic pathways.This review summarizes evidence on the commitment of NRF2 in several mechanisms involved in liver regeneration. Pharmacological stimulation of NRF2 boosts liver mass recovery after partial hepatectomy. Furthermore, when p21 overexpression inhibits hepatocellular proliferation, NRF2 modulates trans-differentiation of cholangiocytes toward hepatocytes. Of interest, activation and differentiation of hepatic progenitors is associated with NRF2 inhibition. Current reports suggest that NRF2 modulation could pave the way for viable therapies to be tested in clinical trials.

article

English

Elsevier, 2023.

Liver regeneration, Partial hepatectomy, Regenerative niche, Redox signaling, Biochemistry, QD415-436