Supplemental Tables S3

<b>Aims: </b>Aurora kinase A (AURKA) has been implicated in promoting myeloid and renal fibrosis. This study aimed to investigate the impact and underlying mechanism of AURKA on liver fibrosis and to assess the therapeutic potential of MLN8237, a small-molecule AURKA inhibitor, in preventing liver fibrosis in mice.<b>Methods: </b>The research used bioinformatics analysis and immunohistochemistry staining on fibrotic liver tissues from human and mouse models to assess AURKA expression. The cellular localization of AURKA was determined through double immunofluorescence staining in human fibrotic liver tissues and primary mouse hepatic stellate cells. RNA interference and AURKA antagonism were used to examine the effects of AURKA on liver fibrosis, while RNA-sequencing, qRT-PCR, and western blotting were employed to elucidate the potential molecular mechanisms of AURKA on hepatic stellate cell activation.<b>Results: </b>The results showed that AURKA was positively correlated with the progression of liver fibrosis and mainly expressed in activated HSCs. Silencing AURKA inhibited HSC activation, proliferation and induced HSC apoptosis, similar to the effects of MLN8237 treatment. Additionally, silencing AURKA suppressed the glycogen synthase kinase-3beta/β-catenin signaling pathway. Pharmacological inhibition of AURKA phosphorylation also reduced liver fibrosis in vivo.<b>Conclusion: </b>In conclusion, AURKA may promote HSC activation and liver fibrosis through the Wnt/β-catenin pathway, suggesting its potential as a therapeutic target for liver fibrosis.

<b>研究目的：</b>极光激酶A（Aurora kinase A, AURKA）已被证实可促进髓系与肾纤维化。本研究旨在探讨AURKA对肝纤维化的影响及其潜在分子机制，并评估小分子AURKA抑制剂MLN8237预防小鼠肝纤维化的治疗潜力。<b>实验方法：</b>本研究通过生物信息学分析及免疫组化染色，检测人源及小鼠纤维化肝组织中AURKA的表达水平；通过对人纤维化肝组织与小鼠原代肝星状细胞（hepatic stellate cells, HSC）开展双重免疫荧光染色，明确AURKA的细胞定位。本研究采用RNA干扰及AURKA拮抗实验，探究AURKA对肝纤维化的调控作用；同时借助RNA测序、qRT-PCR及蛋白质印迹实验，阐明AURKA调控肝星状细胞活化的潜在分子机制。<b>实验结果：</b>结果显示，AURKA的表达水平与肝纤维化进展呈正相关，且主要表达于活化的肝星状细胞中。敲低AURKA可抑制肝星状细胞的活化与增殖，并诱导其凋亡，该效果与MLN8237处理的结果一致。此外，敲低AURKA可抑制糖原合成激酶3β/β-连环蛋白信号通路。药物抑制AURKA磷酸化同样可在体内减轻肝纤维化程度。<b>结论：</b>综上，AURKA可能通过Wnt/β-连环蛋白信号通路促进肝星状细胞活化及肝纤维化，提示其可作为肝纤维化的潜在治疗靶点。