IL-13 as Target to Reduce Cholestasis and Dysbiosis in Abcb4 Knockout Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Model
2.2. Routine Serum Biochemistry
2.3. Histology
2.4. Immunohistochemistry/Immunofluorescence
2.5. Bile Acid Analysis
2.6. Western Blot Analysis
2.7. Transcriptome Microarray and Gene Set Analysis
2.8. Bacterial Translocation to the Liver
2.9. Quantitative Real-Time PCR
2.10. Hepatic Hydroxyproline Ccontent
2.11. 16 SrDNA Sequencing forMicrobiome Profiling
2.12. Bioinformatics Workflow
2.13. Statistical Analysis
3. Results
3.1. IL-13 Knockout Restored Intrahepatic Bile Duct Integrity and Biliary Epithelial Cell Barrier Function in Abcb4−/− Mice
3.2. Reduced Serum BA Improved Liver Integrity
3.3. Lack of IL-13 Reduces Hepatic Pathology and Fibrosis
3.4. IL-13 Alters Hepatic Gene Expression
3.5. Lack of IL-13 Alters Bile Acid Excretion Patterns, Improves Ileal Integrity, and Reduces Bacterial Translocation
3.6. IL-13 Depletion is Associated with Profound Compositional Changes in Gut Microbiota
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Term | Count | p-Value * | Gene Name |
---|---|---|---|
Secondary metabolites biosynthesis, transport, and catabolism | 18 14 | 4.9 × 10−9 1.4× 10−7 | Cyp17a1, Cyp2b13, Cyp2a22, Cyp2c55, Cyp2c67, Cyp2c68, Cyp2g1, Cyp2c37, Cyp26a1, Cyp26b1, Cyp3a11, Cyp3a16, Cyp3a41b, Cyp3a44, Cyp4a10, Cyp4a12b, Cyp4a12a, Cyp4a31, Cyp4f18, Cyp7a1, Cyp7b1 |
Extracellular matrix | 24 26 | 1.2× 10−9 3.0× 10−13 | Adamtsl2, Fras1, Adamts2, Adamts4, Ctsg, Col1a1, Col1a2, Col3a1, Col5a3, Col6a2, Col6a3, Dmbt1, Dpt, Fbn1, Lgals3, Lpl, Lum, Loxl1, Mgp, Mmp12, Mmp13, Mmp2, Mmp3, Mmp7, Mfap4, Mfge8, Slpi, Serpine1, Thbs1, Timp1, Zg16 |
Retinol metabolism | 15 11 | 2.4× 10−7 2.4× 10−5 | Ugt2b37, Cyp2b13, Cyp2c55, Cyp2c68, Cyp2c37, Cyp26a1, Cyp26b1, Cyp3a11, Cyp3a16, Cyp3a41b, Cyp3a44, Cyp4a10, Cyp4a12b, Cyp4a12a, Cyp4a31, Dhrs9 |
PPAR signaling pathway | 13 8 | 3.0× 10−6 1.6× 10−3 | Adipog, Cyp4a10, Cyp4a12b, Cyp4a12a, Cyp4a31, Cyp7a1, Fabp3, Fabp5, Lpl, Plin1, Ppard, Scd1, Scd3, Ucp1 |
Muscle contraction | 9 9 | 1.2× 10−5 2.4× 10−6 | Cacna1s, Lmod3, Myom2, Mybpc1, Myh1, Myh2, Myh4, Myh7, Myl1, Tmod4 |
Cell adhesion | 30 23 | 3.5× 10−5 2.1× 10−4 | Cd24a, Frem1, Ajap1, Cdh1, Clstn2, Clstn3, Cgref1, Cx3cl1, Col6a2, Ctgf, Cxadr, Dpt, Emb, Efs, Flrt1, Flrt3, Fbln7, Fblim1, Itga11, Itga8, Itgax, Lamc3, Lamc2, Mfap4, Mfge8, Myh10, Ncam1, Spp1, Siglecf, Sdk1, Svep1, Thbs1, Tinag, Tnfrsf12a, Ttyh1, Vcam1 |
Steroid hormone biosynthesis | 12 10 | 4.1× 10−5 9.3× 10−5 | Ugt2b37, Cyp17a1, Cyp2b13, Cyp2c55, Cyp2c68, Cyp2c37, Cyp3a11, Cyp3a16, Cyp3a41b, Cyp3a44, Cyp7a1, Cyp7b1, Hsd3b1, Hsd3b5, Sult1e1 |
Focal adhesion | 18 14 | 3.2× 10−4 4.7× 10−4 | Shc2, Actg1, Cav3, Col1a1, Col1a2, Col3a1, Col5a3, Col6a2, Col6a3, Ccnd1, Itga11, Itga8, Jun, Lamc3, Lamc2, Myl2, Pak6, Pdgfa, Spp1, Thbs1 |
ECM receptor interaction | 10 10 | 1.0× 10−3 1.0× 10−4 | Col1a1, Col1a2, Col3a1, Col5a3, Col6a2, Col6a3, Itga11, Itga8, Lamc3, Lamc2, Spp1, Thbs1 |
Chemical carcinogenesis | 10 8 | 1.4× 10−3 3.5× 10−3 | Ugt2b37, Cyp2b13, Cyp2c55, Cyp2c68, Cyp2c37, Cyp3a11, Cyp3a16, Cyp3a41b, Cyp3a44, Gstt3, Sult2a1 |
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Hahn, L.; Helmrich, N.; Herebian, D.; Mayatepek, E.; Drebber, U.; Domann, E.; Olejniczak, S.; Weigel, M.; Hain, T.; Rath, T.; et al. IL-13 as Target to Reduce Cholestasis and Dysbiosis in Abcb4 Knockout Mice. Cells 2020, 9, 1949. https://doi.org/10.3390/cells9091949
Hahn L, Helmrich N, Herebian D, Mayatepek E, Drebber U, Domann E, Olejniczak S, Weigel M, Hain T, Rath T, et al. IL-13 as Target to Reduce Cholestasis and Dysbiosis in Abcb4 Knockout Mice. Cells. 2020; 9(9):1949. https://doi.org/10.3390/cells9091949
Chicago/Turabian StyleHahn, Luisa, Nora Helmrich, Diran Herebian, Ertan Mayatepek, Uta Drebber, Eugen Domann, Stefan Olejniczak, Markus Weigel, Torsten Hain, Timo Rath, and et al. 2020. "IL-13 as Target to Reduce Cholestasis and Dysbiosis in Abcb4 Knockout Mice" Cells 9, no. 9: 1949. https://doi.org/10.3390/cells9091949