Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats
Background: Hirudin has been widely used in the treatment of antifibrosis. Previous studies have shown that hirudin can effectively improve the clinical remission rate of chronic kidney disease. However, the mechanism of its renal protection has not been systematically investigated.Methods: In this...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.741801/full |
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| author | Hang-Xing Yu Hang-Xing Yu Wei Lin Wei Lin Kang Yang Li-Juan Wei Li-Juan Wei Jun-Li Chen Jun-Li Chen Xin-Yue Liu Xin-Yue Liu Ke Zhong Ke Zhong Xin Chen Xin Chen Ming Pei Ming Pei Hong-Tao Yang Hong-Tao Yang |
| author_facet | Hang-Xing Yu Hang-Xing Yu Wei Lin Wei Lin Kang Yang Li-Juan Wei Li-Juan Wei Jun-Li Chen Jun-Li Chen Xin-Yue Liu Xin-Yue Liu Ke Zhong Ke Zhong Xin Chen Xin Chen Ming Pei Ming Pei Hong-Tao Yang Hong-Tao Yang |
| author_sort | Hang-Xing Yu |
| collection | DOAJ |
| description | Background: Hirudin has been widely used in the treatment of antifibrosis. Previous studies have shown that hirudin can effectively improve the clinical remission rate of chronic kidney disease. However, the mechanism of its renal protection has not been systematically investigated.Methods: In this study, the reliability of UUO-induced renal interstitial fibrosis was evaluated by histopathological verification. High-throughput transcriptome sequencing was used to elucidate the molecular mechanism of hirudin, differentially expressed mRNAs were identified, and their functions were analyzed by GO analysis and GSEA. In addition, the RNA-seq results were validated by in vitro and vivo experiments.Results: We found 322 identical differential expressed genes (IDEs) in the UUO hirudin-treated group compared with the sham group. Functional enrichment analysis indicated that cellular amino acid metabolic processes were the most obvious enrichment pathways in biological processes. In terms of molecular functional enrichment analysis, IDEs were mainly enriched in coenzyme binding, pyridoxal phosphate binding and other pathways. In addition, microbody is the most obvious pathway for cellular components. A total of 115 signaling pathways were enriched, and AMPK, JAK-STAT, and PI3K-Akt signaling pathways were the important signaling pathways enriched. We found that PI3K, p-Akt, and mTOR expression were significantly reduced by hirudin treatment. In particular, our results showed that hirudin could induce a decrease in the expression of autophagy-related proteins such as P62, LC3, Beclin-1 in TGF-β1-induced NRK-52E cells.Conclusion: Our results suggest that hirudin may protect the kidney by ameliorating renal autophagy impairment through modulating the PI3K/Akt pathway. |
| first_indexed | 2024-12-16T11:16:28Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-16T11:16:28Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-d4a8a85b21a7403387692ae2c3dd43e22022-12-21T22:33:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.741801741801Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO RatsHang-Xing Yu0Hang-Xing Yu1Wei Lin2Wei Lin3Kang Yang4Li-Juan Wei5Li-Juan Wei6Jun-Li Chen7Jun-Li Chen8Xin-Yue Liu9Xin-Yue Liu10Ke Zhong11Ke Zhong12Xin Chen13Xin Chen14Ming Pei15Ming Pei16Hong-Tao Yang17Hong-Tao Yang18Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaKidney Disease Treatment Center, The First Affiliated Hospital of Henan University of CM, Zhengzhou, ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaBackground: Hirudin has been widely used in the treatment of antifibrosis. Previous studies have shown that hirudin can effectively improve the clinical remission rate of chronic kidney disease. However, the mechanism of its renal protection has not been systematically investigated.Methods: In this study, the reliability of UUO-induced renal interstitial fibrosis was evaluated by histopathological verification. High-throughput transcriptome sequencing was used to elucidate the molecular mechanism of hirudin, differentially expressed mRNAs were identified, and their functions were analyzed by GO analysis and GSEA. In addition, the RNA-seq results were validated by in vitro and vivo experiments.Results: We found 322 identical differential expressed genes (IDEs) in the UUO hirudin-treated group compared with the sham group. Functional enrichment analysis indicated that cellular amino acid metabolic processes were the most obvious enrichment pathways in biological processes. In terms of molecular functional enrichment analysis, IDEs were mainly enriched in coenzyme binding, pyridoxal phosphate binding and other pathways. In addition, microbody is the most obvious pathway for cellular components. A total of 115 signaling pathways were enriched, and AMPK, JAK-STAT, and PI3K-Akt signaling pathways were the important signaling pathways enriched. We found that PI3K, p-Akt, and mTOR expression were significantly reduced by hirudin treatment. In particular, our results showed that hirudin could induce a decrease in the expression of autophagy-related proteins such as P62, LC3, Beclin-1 in TGF-β1-induced NRK-52E cells.Conclusion: Our results suggest that hirudin may protect the kidney by ameliorating renal autophagy impairment through modulating the PI3K/Akt pathway.https://www.frontiersin.org/articles/10.3389/fphar.2021.741801/fullrenal fibrosis (RF)natural productshirudin (PubChem CID: 72941487)transcriptome (RNA-seq)UUO (unilateral ureteral obstruction) |
| spellingShingle | Hang-Xing Yu Hang-Xing Yu Wei Lin Wei Lin Kang Yang Li-Juan Wei Li-Juan Wei Jun-Li Chen Jun-Li Chen Xin-Yue Liu Xin-Yue Liu Ke Zhong Ke Zhong Xin Chen Xin Chen Ming Pei Ming Pei Hong-Tao Yang Hong-Tao Yang Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats Frontiers in Pharmacology renal fibrosis (RF) natural products hirudin (PubChem CID: 72941487) transcriptome (RNA-seq) UUO (unilateral ureteral obstruction) |
| title | Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats |
| title_full | Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats |
| title_fullStr | Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats |
| title_full_unstemmed | Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats |
| title_short | Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats |
| title_sort | transcriptome based network analysis reveals hirudin potentiates anti renal fibrosis efficacy in uuo rats |
| topic | renal fibrosis (RF) natural products hirudin (PubChem CID: 72941487) transcriptome (RNA-seq) UUO (unilateral ureteral obstruction) |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.741801/full |
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