**1. Introduction**

The liver is a unique organ with the ability to completely regenerate to the original size after massive loss. Seventy percent partial hepatectomy is the standard model for studying normal liver

regeneration. [1] The orchestrated complex process involves a cytokine, growth factor, and metabolic network [2], among which the cytokine network is initiated through the binding of tumor necrosis factor (TNF) to TNF receptor 1 (TNFR1), which leads to the activation of nuclear factor (NF)-κB in nonparenchymal cells, the production of interleukin (IL)-6, and the activation of signal transducer and activator of transcription 3 (STAT3) in hepatocytes [2]. In fact, TNFR1–/– mice showed delayed regeneration attributed to ine fficient activation of NF-κB [3].

Restoration of liver mass involves the proliferation of hepatocytes and nonparenchymal cells. Angiogenesis is essential for successful liver regeneration. [4–7] Mutual growth-regulatory signaling interactions between hepatocytes and endothelial cells during liver regeneration after 70% partial hepatectomy involve vascular endothelial growth factor (VEGF), IL-6, transforming growth factor (TGF) α, fibroblast growth factor (FGF) 1, and hepatocyte growth factor (HGF) [5]. Thus, interactions of multiple pathways during liver regeneration are evolutionarily preserved for host survival.

B-cell activating factor (BAFF) is a type II transmembrane glycoprotein that belongs to the TNF super family [8]. BAFF-mediated signaling involves B-cell CCL/lymphoma 10 (BCL10) nuclear translocation, changes in phospho-AKT levels, and NF-κB transactivity [9,10]. BCL10-related signaling controls the growth of cervical cancer cells via NF-κB-dependent cyclin D1 regulation [11]. Three BAFF receptors (BAFF-R, transmembrane activator and CAML interactor (TACI), and B-cell maturation antigen (BCMA)), which can specifically activate B lymphocytes and promote their proliferation, have been identified [12].

The clinical significance of BAFF is found with serum BAFF levels in patients with nonalcoholic steatohepatitis (NASH) patients had higher levels than patients with simple steatosis; meanwhile, the histological findings also demonstrated that higher BAFF levels were associated with the presence of hepatocyte ballooning and advanced fibrosis [13]. Furthermore, BAFF was also found to have a protective role in hepatic steatosis via down regulating the expression of steatogenesis genes and enhancing steatosis in hepatocytes through BAFF-R [14]. However, the role of BAFF in liver regeneration has not ye<sup>t</sup> been fully elucidated.

Accordingly, we hypothesize that BAFF might play a role in liver regeneration after 70% partial hepatectomy. In this study, we investigated the role of BAFF in liver regeneration. Our findings provided important insights into the role of BAFF in angiogenesis and liver regeneration.
