Characterization of aggrephagy-related genes to predict the progression of liver fibrosis from multi-omics profiles
Background: Liver fibrosis is recognized as a consequence of persistent liver damage. Hence, understanding the mechanisms of liver fibrosis could help patients reverse this process. Aggrephagy is a selective type of autophagy which is under study in various diseases. However, the investigation of ag...
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KeAi Communications Co., Ltd.
2024-03-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949723X23000302 |
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| author | Jing Chen Zi-Cheng Zhou Yang Yan Shu-Zhen Wu Tao Ma Han Xuan Ruo-Chun Wang Chi-Yu Gu Yi-Heng Liu Qing-Qing Liu Si-Jia Ge Wei Huang Cui-Hua Lu |
| author_facet | Jing Chen Zi-Cheng Zhou Yang Yan Shu-Zhen Wu Tao Ma Han Xuan Ruo-Chun Wang Chi-Yu Gu Yi-Heng Liu Qing-Qing Liu Si-Jia Ge Wei Huang Cui-Hua Lu |
| author_sort | Jing Chen |
| collection | DOAJ |
| description | Background: Liver fibrosis is recognized as a consequence of persistent liver damage. Hence, understanding the mechanisms of liver fibrosis could help patients reverse this process. Aggrephagy is a selective type of autophagy which is under study in various diseases. However, the investigation of aggrephagy in liver fibrosis has not been reported yet. Methods: Five GEO databases were first batched into an integrated dataset by PCA analysis and facilitated for exploration of the aggrephagy-related genes. In addition, the diagnostic model under the aggrephagy-related genes was constructed by random forest. Then Western blot and immunofluorescence were employed in cells treated by autophagy-inhibitor Bafilomycin A1 to analyze whether the aggrephagy induced by liver fibrosis is necessary for aggregates degradation. Furthermore, the single cell data from GEO database and AUCell analysis functioned to detect the aggrephagy score. CellChat analysis compared the interaction strength and underlying receptor ligands between the different aggrephagy score groups. Furthermore, we used the monocle function to display the dynamic process from low aggrephagy score to high aggrephagy score groups. Finally, we used the consensus cluster to compare the clinical characteristics and underlying drug compounds under aggrephagy-score. Results: First, we observed that aggrephagy score was much higher in the liver fibrosis group than in the normal group. Then our results showed that aggrephagy score was positively correlated with several metabolism pathways. In addition, aggrephagy related diagnostic model showed higher efficiency than other markers of liver fibrosis. Further experiments revealed that the removal of aggregates in liver fibrosis was depended on aggrephagy. We then observed that aggrephagy score and CFTR levels were dominantly located in hepatocytes from single-cell data. Moreover, the high aggrephagy-score group showed increased cell interaction strength, intercellular receptor-ligand signaling, and the transcription factor activity of HNF1B than the low aggrephagy-score groups. Hence, aggrephagy might be a promising target for liver fibrosis. Conclusions: Our results showed that the aggrephagy score is a promising index for diagnosing liver fibrosis. |
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| spelling | doaj.art-42926864a385446fbdfd55cd579e224f2024-07-05T04:17:32ZengKeAi Communications Co., Ltd.Biomedical Technology2949-723X2024-03-0154659Characterization of aggrephagy-related genes to predict the progression of liver fibrosis from multi-omics profilesJing Chen0Zi-Cheng Zhou1Yang Yan2Shu-Zhen Wu3Tao Ma4Han Xuan5Ruo-Chun Wang6Chi-Yu Gu7Yi-Heng Liu8Qing-Qing Liu9Si-Jia Ge10Wei Huang11Cui-Hua Lu12Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China; Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China; Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China; Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China; Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Gastroenterology, Nantong City No 1 People's Hospital and Second Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, ChinaDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China; Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, China; Corresponding author. Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China.Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China; Corresponding author.Background: Liver fibrosis is recognized as a consequence of persistent liver damage. Hence, understanding the mechanisms of liver fibrosis could help patients reverse this process. Aggrephagy is a selective type of autophagy which is under study in various diseases. However, the investigation of aggrephagy in liver fibrosis has not been reported yet. Methods: Five GEO databases were first batched into an integrated dataset by PCA analysis and facilitated for exploration of the aggrephagy-related genes. In addition, the diagnostic model under the aggrephagy-related genes was constructed by random forest. Then Western blot and immunofluorescence were employed in cells treated by autophagy-inhibitor Bafilomycin A1 to analyze whether the aggrephagy induced by liver fibrosis is necessary for aggregates degradation. Furthermore, the single cell data from GEO database and AUCell analysis functioned to detect the aggrephagy score. CellChat analysis compared the interaction strength and underlying receptor ligands between the different aggrephagy score groups. Furthermore, we used the monocle function to display the dynamic process from low aggrephagy score to high aggrephagy score groups. Finally, we used the consensus cluster to compare the clinical characteristics and underlying drug compounds under aggrephagy-score. Results: First, we observed that aggrephagy score was much higher in the liver fibrosis group than in the normal group. Then our results showed that aggrephagy score was positively correlated with several metabolism pathways. In addition, aggrephagy related diagnostic model showed higher efficiency than other markers of liver fibrosis. Further experiments revealed that the removal of aggregates in liver fibrosis was depended on aggrephagy. We then observed that aggrephagy score and CFTR levels were dominantly located in hepatocytes from single-cell data. Moreover, the high aggrephagy-score group showed increased cell interaction strength, intercellular receptor-ligand signaling, and the transcription factor activity of HNF1B than the low aggrephagy-score groups. Hence, aggrephagy might be a promising target for liver fibrosis. Conclusions: Our results showed that the aggrephagy score is a promising index for diagnosing liver fibrosis.http://www.sciencedirect.com/science/article/pii/S2949723X23000302Liver fibrosisAggrephagyHepatocytesCFTRSingle cell |
| spellingShingle | Jing Chen Zi-Cheng Zhou Yang Yan Shu-Zhen Wu Tao Ma Han Xuan Ruo-Chun Wang Chi-Yu Gu Yi-Heng Liu Qing-Qing Liu Si-Jia Ge Wei Huang Cui-Hua Lu Characterization of aggrephagy-related genes to predict the progression of liver fibrosis from multi-omics profiles Biomedical Technology Liver fibrosis Aggrephagy Hepatocytes CFTR Single cell |
| title | Characterization of aggrephagy-related genes to predict the progression of liver fibrosis from multi-omics profiles |
| title_full | Characterization of aggrephagy-related genes to predict the progression of liver fibrosis from multi-omics profiles |
| title_fullStr | Characterization of aggrephagy-related genes to predict the progression of liver fibrosis from multi-omics profiles |
| title_full_unstemmed | Characterization of aggrephagy-related genes to predict the progression of liver fibrosis from multi-omics profiles |
| title_short | Characterization of aggrephagy-related genes to predict the progression of liver fibrosis from multi-omics profiles |
| title_sort | characterization of aggrephagy related genes to predict the progression of liver fibrosis from multi omics profiles |
| topic | Liver fibrosis Aggrephagy Hepatocytes CFTR Single cell |
| url | http://www.sciencedirect.com/science/article/pii/S2949723X23000302 |
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