Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine Pathway
Background: Pulmonary Fibrosis (PF) is an interstitial lung disease characterized by excessive accumulation of extracellular matrix in the lungs, which disrupts the structure and gas exchange of the alveoli. There are only two approved therapies for PF, nintedanib (Nib) and pirfenidone. Therefore, t...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-04-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.661129/full |
| _version_ | 1818972474583285760 |
|---|---|
| author | Lili Zhang Sihao Qu Lu Wang Chunguo Wang Qinghe Yu Zhimin Zhang Yirui Diao Binbin Zhang Yadong Li Yuanyuan Shi Yuanyuan Shi Peng Wang |
| author_facet | Lili Zhang Sihao Qu Lu Wang Chunguo Wang Qinghe Yu Zhimin Zhang Yirui Diao Binbin Zhang Yadong Li Yuanyuan Shi Yuanyuan Shi Peng Wang |
| author_sort | Lili Zhang |
| collection | DOAJ |
| description | Background: Pulmonary Fibrosis (PF) is an interstitial lung disease characterized by excessive accumulation of extracellular matrix in the lungs, which disrupts the structure and gas exchange of the alveoli. There are only two approved therapies for PF, nintedanib (Nib) and pirfenidone. Therefore, the use of Chinese medicine for PF is attracting attention. Tianlongkechuanling (TL) is an effective Chinese formula that has been applied clinically to alleviate PF, which can enhance lung function and quality of life.Purpose: The potential effects and specific mechanisms of TL have not been fully explored, yet. In the present study, proteomics was performed to explore the therapeutic protein targets of TL on Bleomycin (BLM)-induced Pulmonary Fibrosis.Method: BLM-induced PF mice models were established. Hematoxylineosin staining and Masson staining were used to analyze histopathological changes and collagen deposition. To screen the differential proteins expression between the Control, BLM, BLM + TL and BLM + Nib (BLM + nintedanib) groups, quantitative proteomics was performed using tandem mass tag (TMT) labeling with nanoLC-MS/MS [nano liquid chromatographymass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein–protein interactions (PPI) were established by STRING. Expressions of α-smooth muscle actin (α-SMA), Collagen I (Col1a1), Fibronectin (Fn1) and enzymes in arginase-ornithine pathway were detected by Western blot or RT-PCR.Result: TL treatments significantly ameliorated BLM-induced collagen deposition in lung tissues. Moreover, TL can inhibit the protein expressions of α-SMA and the mRNA expressions of Col1a1 and Fn1. Using TMT technology, we observed 253 differentially expressed proteins related to PPI networks and involved different KEGG pathways. Arginase-ornithine pathway is highly significant. The expression of arginase1 (Arg1), carbamoyltransferase (OTC), carbamoy-phosphate synthase (CPS1), argininosuccinate synthase (ASS1), ornithine aminotransferase (OAT) argininosuccinate lyase (ASL) and inducible nitric oxide synthase (iNOS) was significantly decreased after TL treatments.Conclusion: Administration of TL in BLM-induced mice resulted in decreasing pulmonary fibrosis. Our findings propose that the down regulation of arginase-ornithine pathway expression with the reduction of arginase biosynthesis is a central mechanism and potential treatment for pulmonary fibrosis with the prevention of TL. |
| first_indexed | 2024-12-20T15:08:51Z |
| format | Article |
| id | doaj.art-47b79adffb994d11968841a9b4d9091c |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T15:08:51Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-47b79adffb994d11968841a9b4d9091c2022-12-21T19:36:23ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.661129661129Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine PathwayLili Zhang0Sihao Qu1Lu Wang2Chunguo Wang3Qinghe Yu4Zhimin Zhang5Yirui Diao6Binbin Zhang7Yadong Li8Yuanyuan Shi9Yuanyuan Shi10Peng Wang11School of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaTraditional Chinese Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaTraditional Chinese Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaShenzhen Research Institute, Beijing University of Chinese Medicine, Shenzhen, ChinaTraditional Chinese Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaBackground: Pulmonary Fibrosis (PF) is an interstitial lung disease characterized by excessive accumulation of extracellular matrix in the lungs, which disrupts the structure and gas exchange of the alveoli. There are only two approved therapies for PF, nintedanib (Nib) and pirfenidone. Therefore, the use of Chinese medicine for PF is attracting attention. Tianlongkechuanling (TL) is an effective Chinese formula that has been applied clinically to alleviate PF, which can enhance lung function and quality of life.Purpose: The potential effects and specific mechanisms of TL have not been fully explored, yet. In the present study, proteomics was performed to explore the therapeutic protein targets of TL on Bleomycin (BLM)-induced Pulmonary Fibrosis.Method: BLM-induced PF mice models were established. Hematoxylineosin staining and Masson staining were used to analyze histopathological changes and collagen deposition. To screen the differential proteins expression between the Control, BLM, BLM + TL and BLM + Nib (BLM + nintedanib) groups, quantitative proteomics was performed using tandem mass tag (TMT) labeling with nanoLC-MS/MS [nano liquid chromatographymass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein–protein interactions (PPI) were established by STRING. Expressions of α-smooth muscle actin (α-SMA), Collagen I (Col1a1), Fibronectin (Fn1) and enzymes in arginase-ornithine pathway were detected by Western blot or RT-PCR.Result: TL treatments significantly ameliorated BLM-induced collagen deposition in lung tissues. Moreover, TL can inhibit the protein expressions of α-SMA and the mRNA expressions of Col1a1 and Fn1. Using TMT technology, we observed 253 differentially expressed proteins related to PPI networks and involved different KEGG pathways. Arginase-ornithine pathway is highly significant. The expression of arginase1 (Arg1), carbamoyltransferase (OTC), carbamoy-phosphate synthase (CPS1), argininosuccinate synthase (ASS1), ornithine aminotransferase (OAT) argininosuccinate lyase (ASL) and inducible nitric oxide synthase (iNOS) was significantly decreased after TL treatments.Conclusion: Administration of TL in BLM-induced mice resulted in decreasing pulmonary fibrosis. Our findings propose that the down regulation of arginase-ornithine pathway expression with the reduction of arginase biosynthesis is a central mechanism and potential treatment for pulmonary fibrosis with the prevention of TL.https://www.frontiersin.org/articles/10.3389/fphar.2021.661129/fullproteomicstianlong kechuanlingpulmonary fibrosisarginasearginase-ornithine pathway |
| spellingShingle | Lili Zhang Sihao Qu Lu Wang Chunguo Wang Qinghe Yu Zhimin Zhang Yirui Diao Binbin Zhang Yadong Li Yuanyuan Shi Yuanyuan Shi Peng Wang Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine Pathway Frontiers in Pharmacology proteomics tianlong kechuanling pulmonary fibrosis arginase arginase-ornithine pathway |
| title | Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine Pathway |
| title_full | Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine Pathway |
| title_fullStr | Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine Pathway |
| title_full_unstemmed | Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine Pathway |
| title_short | Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine Pathway |
| title_sort | tianlongkechuanling inhibits pulmonary fibrosis through down regulation of arginase ornithine pathway |
| topic | proteomics tianlong kechuanling pulmonary fibrosis arginase arginase-ornithine pathway |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.661129/full |
| work_keys_str_mv | AT lilizhang tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT sihaoqu tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT luwang tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT chunguowang tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT qingheyu tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT zhiminzhang tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT yiruidiao tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT binbinzhang tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT yadongli tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT yuanyuanshi tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT yuanyuanshi tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway AT pengwang tianlongkechuanlinginhibitspulmonaryfibrosisthroughdownregulationofarginaseornithinepathway |