Vosough Massoud, Shokouhian Bahare, Sharbaf Mohammad Amin, Solhi Roya, Heidari Zahra, Seydi Homeyra, Hassan Moustapha, Devaraj Ezhilarasan, Najimi Mustapha
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Hepatol Commun. 2025 Apr 30;9(5). doi: 10.1097/HC9.0000000000000692. eCollection 2025 May 1.
The liver has a unique ability to regenerate to meet the body's metabolic needs, even following acute or chronic injuries. The cellular and molecular mechanisms underlying normal liver regeneration have been well investigated to improve organ transplantation outcomes. Once liver regeneration is impaired, pathological regeneration occurs, and the underlying cellular and molecular mechanisms require further investigations. Nevertheless, a plethora of cytokines and growth factor-mediated pathways have been reported to modulate physiological and pathological liver regeneration. Regenerative mitogens play an essential role in hepatocyte proliferation. Accelerator mitogens in synergism with regenerative ones promote liver regeneration following hepatectomy. Finally, terminator mitogens restore the proliferating status of hepatocytes to a differentiated and quiescent state upon completion of regeneration. Chronic loss of hepatocytes, which can manifest in chronic liver disorders of any etiology, often has undesired structural consequences, including fibrosis, cirrhosis, and liver neoplasia due to the unregulated proliferation of remaining hepatocytes. In fact, any impairment in the physiological function of the terminator mitogens results in the progression of pathological liver regeneration. In the current review, we intend to highlight the updated cellular and molecular mechanisms involved in liver regeneration and discuss the impairments in central regulating mechanisms responsible for pathological liver regeneration.
肝脏具有独特的再生能力，即使在急性或慢性损伤后也能满足身体的代谢需求。为了改善器官移植的结果，人们对正常肝脏再生的细胞和分子机制进行了深入研究。一旦肝脏再生受损，就会发生病理性再生，其潜在的细胞和分子机制需要进一步研究。然而，据报道，大量细胞因子和生长因子介导的途径可调节生理性和病理性肝脏再生。再生有丝分裂原在肝细胞增殖中起重要作用。促进有丝分裂原与再生有丝分裂原协同作用，促进肝切除术后的肝脏再生。最后，终止有丝分裂原在再生完成后将肝细胞的增殖状态恢复到分化和静止状态。肝细胞的慢性丢失可表现为任何病因的慢性肝脏疾病，由于剩余肝细胞的不受控制的增殖，常常会产生不良的结构后果，包括纤维化、肝硬化和肝肿瘤。事实上，终止有丝分裂原的生理功能的任何损害都会导致病理性肝脏再生的进展。在本综述中，我们旨在强调肝脏再生中涉及的最新细胞和分子机制，并讨论负责病理性肝脏再生的中央调节机制中的损害。
