Aurora kinase A promotes hepatic stellate cell activation and liver fibrosis through the Wnt/β-catenin pathway
AimsAurora 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 i...
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| Format: | Article |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1517226/full |
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| author | Guanqi Dai Guanqi Dai Junhao Lin Yuchuan Jiang Yuchuan Jiang Xinhui Liu Peng Chen Yixiao Zhang Zhenghui Song Xuefen Zhuang Jinge Cong Yingchun Li Xuanjia Hong Yun Liu Dong Xiao Dong Xiao Aimin Li Yue Luo |
| author_facet | Guanqi Dai Guanqi Dai Junhao Lin Yuchuan Jiang Yuchuan Jiang Xinhui Liu Peng Chen Yixiao Zhang Zhenghui Song Xuefen Zhuang Jinge Cong Yingchun Li Xuanjia Hong Yun Liu Dong Xiao Dong Xiao Aimin Li Yue Luo |
| author_sort | Guanqi Dai |
| collection | DOAJ |
| description | AimsAurora 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.MethodsThe 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.ResultsThe results showed that AURKA was positively correlated with the progression of liver fibrosis and was predominantly expressed in activated HSCs. Silencing AURKA inhibited HSC activation and proliferation, and induced HSC apoptosis, effects that were similar to those observed with MLN8237 treatment. Additionally, silencing AURKA suppressed the glycogen synthase kinase-3β/β-catenin signaling pathway. Pharmacological inhibition of AURKA phosphorylation also resulted in reduced liver fibrosis in vivo.ConclusionIn 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. |
| format | Article |
| id | doaj-art-58610eaaa7c340e88cca949f9c99ad7e |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-58610eaaa7c340e88cca949f9c99ad7e2025-01-06T05:13:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15172261517226Aurora kinase A promotes hepatic stellate cell activation and liver fibrosis through the Wnt/β-catenin pathwayGuanqi Dai0Guanqi Dai1Junhao Lin2Yuchuan Jiang3Yuchuan Jiang4Xinhui Liu5Peng Chen6Yixiao Zhang7Zhenghui Song8Xuefen Zhuang9Jinge Cong10Yingchun Li11Xuanjia Hong12Yun Liu13Dong Xiao14Dong Xiao15Aimin Li16Yue Luo17Department of Radiotherapy, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaCancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, ChinaDepartment of Radiotherapy, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Radiotherapy, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Radiotherapy, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaCancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, ChinaDepartment of Radiotherapy, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Radiotherapy, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaCancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, ChinaCancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, ChinaCancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, ChinaDepartment of Endocrinology and Metabolic Diseases, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, ChinaCancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, ChinaLaboratory Animal Center, Southern Medical University, Guangzhou, ChinaDepartment of Radiotherapy, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Radiotherapy, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaAimsAurora 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.MethodsThe 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.ResultsThe results showed that AURKA was positively correlated with the progression of liver fibrosis and was predominantly expressed in activated HSCs. Silencing AURKA inhibited HSC activation and proliferation, and induced HSC apoptosis, effects that were similar to those observed with MLN8237 treatment. Additionally, silencing AURKA suppressed the glycogen synthase kinase-3β/β-catenin signaling pathway. Pharmacological inhibition of AURKA phosphorylation also resulted in reduced liver fibrosis in vivo.ConclusionIn 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.https://www.frontiersin.org/articles/10.3389/fonc.2024.1517226/fullAurora kinase Ahepatic stellate cellsliver fibrosisMLN8237Wnt/β-catenin pathway |
| spellingShingle | Guanqi Dai Guanqi Dai Junhao Lin Yuchuan Jiang Yuchuan Jiang Xinhui Liu Peng Chen Yixiao Zhang Zhenghui Song Xuefen Zhuang Jinge Cong Yingchun Li Xuanjia Hong Yun Liu Dong Xiao Dong Xiao Aimin Li Yue Luo Aurora kinase A promotes hepatic stellate cell activation and liver fibrosis through the Wnt/β-catenin pathway Frontiers in Oncology Aurora kinase A hepatic stellate cells liver fibrosis MLN8237 Wnt/β-catenin pathway |
| title | Aurora kinase A promotes hepatic stellate cell activation and liver fibrosis through the Wnt/β-catenin pathway |
| title_full | Aurora kinase A promotes hepatic stellate cell activation and liver fibrosis through the Wnt/β-catenin pathway |
| title_fullStr | Aurora kinase A promotes hepatic stellate cell activation and liver fibrosis through the Wnt/β-catenin pathway |
| title_full_unstemmed | Aurora kinase A promotes hepatic stellate cell activation and liver fibrosis through the Wnt/β-catenin pathway |
| title_short | Aurora kinase A promotes hepatic stellate cell activation and liver fibrosis through the Wnt/β-catenin pathway |
| title_sort | aurora kinase a promotes hepatic stellate cell activation and liver fibrosis through the wnt β catenin pathway |
| topic | Aurora kinase A hepatic stellate cells liver fibrosis MLN8237 Wnt/β-catenin pathway |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1517226/full |
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