IL-6 Trans-signaling Controls Liver Regeneration After Partial Hepatectomy

The process of liver regeneration following partial hepatectomy is a remarkable physiological response that involves intricate molecular mechanisms. Among the key players in this regenerative process is interleukin-6 (IL-6), a multifunctional cytokine known for its diverse roles in immune and inflammatory responses. IL-6 signals through two distinct pathways: the classical pathway, involving the membrane-bound IL-6 receptor (IL-6R), and the trans-signaling pathway, which relies on a soluble form of IL-6R. However, the specific contributions of these pathways to liver regeneration have remained elusive.

This study aimed to unravel the specific roles of IL-6 trans-signaling in the context of liver regeneration after partial hepatectomy. Using a novel transgenic mouse model with selective IL-6 trans-signaling activation, we systematically investigated the impact of this pathway on hepatocyte proliferation and tissue repair. Our findings unequivocally demonstrate that IL-6 trans-signaling is a critical regulator of liver regeneration. In terms of mechanisms, we demonstrated that IL-6 trans-signaling triggers the synthesis of hepatocyte growth factor from hepatic stellate cells, culminating in the stimulation of hepatocyte proliferation and facilitating tissue repair.

These findings have significant implications for therapeutic strategies aimed at promoting liver regeneration in the context of liver injury and disease. By elucidating the precise contributions of IL-6 trans-signaling to liver regeneration, this study not only enhances our understanding of fundamental regenerative processes but also highlights potential targets for interventions to enhance tissue repair and recovery. Our work underscores the importance of dissecting specific signaling pathways in deciphering complex biological phenomena and advancing translational research for clinical benefit.

 

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Publication History

Article published online:
23 January 2024