Omega-Class Glutathione Transferases of Carcinogenic Liver Fluke, Clonorchis sinensis, Modulate Apoptosis and Differentiation of Host Cholangiocytes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Rat Biliary Ductal Epithelium Experimentally Infected with C. sinensis
2.2. Expression of rCsGSTos
2.3. Antisera
2.4. HIBEC Culture and Uptake of rCsGSTos
2.5. Oxidative Stress
2.6. Quantitative RNA Sequencing (Quant-RNAseq)
2.7. Quantitative Real Time Reverse Transcription-PCR (qRT-PCR)
2.8. Data Analysis
2.9. Double Sandwich-ELISA
2.10. Cell Viability
2.11. Fluorescence-Activated Cell Sorting (FACS) Analysis
2.12. Western Blot Analysis
2.13. Immunohistochemical Staining
2.14. Statistical Analysis
3. Results
3.1. CsGSTo1 and CsGSTo2 Are Accumulated in Host Cholangiocytes In Vivo and In Vitro
3.2. rCsGSTos Inhibit Oxidative Stress-Induced Apoptosis
3.3. Functional Characterization of the Altered HIBEC Intracellular Environment in Response to rCsGSTos
3.4. rCsGSTos Augment Cholangiocyte Survival through Activation of Src-PI3K/Akt-NF-κB p65 Signal Pathway Followed by Expressional Regulation of Genes Engaged in Apoptotic Process
3.5. rCsGSTos Induce Phosphorylation of MKK3/6 and p38 MAPK, thus Regulate the Expression of Genes Involved in Cell Differentiation and Are Located in the C. sinensis Infected Biliary Ductal Epithelium Where Cytokeratin 19 Is Expressed
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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KEGG ID | Signaling Pathways a | No. of Gene | Related Genes |
---|---|---|---|
hsa04621 | NOD-like receptor | 10 | NEK7, CXCL1, CXCL3, IRF7, OAS1, OAS2, OAS3, CCL5, STAT1, CASP8b |
hsa04064 | NF-kappa B | 9 | GADD45G, EDARADD, CXCL1, CXCL3, ICAM1, PIDD1, PTGS2, BCL2A1, TNFSF11 |
hsa04010 | MAPK | 8 | GADD45G, DUSP8, EPHA2, MECOM, HSPA1L, HSPA6, MAPK7, MAPK8IP1 |
hsa04657 | IL-17 | 7 | CSF3c, CXCL1, CXCL3, IL17D, MAPK7, PTGS2, CASP8 |
hsa04115 | p53 | 6 | GADD45G, CD82, PIDD1, CASP8, CCNB2, CDK1 |
hsa04668 | TNF | 6 | CXCL1, CXCL3, ICAM1, PTGS2, CCL5, CASP8 |
hsa04630 | JAK/STAT | 5 | IL24, CSF3, IL11, IL17D, STAT1 |
hsa04071 | Sphingolipid | 5 | S1PR1, S1PR3, CERS2, ABCC1, BDKRB2 |
hsa04020 | Calcium | 4 | AGTR1, EDNRB, PHKG2, BDKRB2 |
hsa04620 | Toll-like receptor | 4 | IRF7, CCL5, STAT1, CASP8 |
hsa04922 | Glucagon | 4 | SIK1, CRTC2, PHKG2, PPP4C |
hsa04915 | Estrogen | 4 | HBEGF, HSPA1L, HSPA6, KRT15 |
hsa04062 | Chemokine | 4 | CXCL1, CXCL3, CCL5, STAT1 |
hsa04625 | C-type lectin receptor | 4 | IL17D, PTGS2, STAT1, CASP8 |
hsa04068 | FoxO | 4 | PLK4, GADD45G, S1PR1, CCNB2 |
hsa04622 | RIG-I-like receptor | 3 | IRF7, CASP8, ISG15 |
hsa04151 | PI3K/Akt | 3 | CSF3, EPHA2, CRTC2 |
hsa03320 | PPAR | 3 | ANGPTL4, ACSL5, PPARG |
hsa04022 | cGMP/PKG | 3 | AGTR1, EDNRB, BDKRB2 |
hsa04921 | Oxytocin | 3 | KCNJ2, MAPK7, PTGS2 |
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Ahn, C.-S.; Kim, J.-G.; Kang, I.; Kong, Y. Omega-Class Glutathione Transferases of Carcinogenic Liver Fluke, Clonorchis sinensis, Modulate Apoptosis and Differentiation of Host Cholangiocytes. Antioxidants 2021, 10, 1017. https://doi.org/10.3390/antiox10071017
Ahn C-S, Kim J-G, Kang I, Kong Y. Omega-Class Glutathione Transferases of Carcinogenic Liver Fluke, Clonorchis sinensis, Modulate Apoptosis and Differentiation of Host Cholangiocytes. Antioxidants. 2021; 10(7):1017. https://doi.org/10.3390/antiox10071017
Chicago/Turabian StyleAhn, Chun-Seob, Jeong-Geun Kim, Insug Kang, and Yoon Kong. 2021. "Omega-Class Glutathione Transferases of Carcinogenic Liver Fluke, Clonorchis sinensis, Modulate Apoptosis and Differentiation of Host Cholangiocytes" Antioxidants 10, no. 7: 1017. https://doi.org/10.3390/antiox10071017
APA StyleAhn, C.-S., Kim, J.-G., Kang, I., & Kong, Y. (2021). Omega-Class Glutathione Transferases of Carcinogenic Liver Fluke, Clonorchis sinensis, Modulate Apoptosis and Differentiation of Host Cholangiocytes. Antioxidants, 10(7), 1017. https://doi.org/10.3390/antiox10071017