Glycochenodeoxycholate Promotes Liver Fibrosis in Mice with Hepatocellular Cholestasis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Experiments
2.2. Serum Biochemistry and Serum Bile Salt Measurements
2.3. Liver Histology, Immunohistochemistry, and Hydroxyproline Quantification
2.4. Hepatic Stellate Cell Isolation and Culture
2.5. Collagen Quantification In Vitro
2.6. Quantitative Real-Time PCR
2.7. Western Blotting
2.8. Statistics
3. Results
3.1. Bile Salt Feeding Induces Chronic Cholestasis in Atp8b1G308V/G308V Mice without Relevant Liver Damage
3.2. GCDCA Feeding Induces a “Humanized” Bile Salt Pool
3.3. Chronic Cholestasis, upon Supplementation of GCDCA, Induces Liver Fibrosis in Atp8b1G308V/G308V Mice
3.4. Hydrophobic, but Not Hydrophilic, Bile Salts Promote Proliferation and Collagen Deposition by Primary HSCs
3.5. Bile-Salt-Induced HSC Proliferation is Associated with Activation of the MEK/Erk Signaling Cascade
3.6. Bile-Salt-Induced HSC Proliferation and Collagen Deposition Is Diminished by MEK/Erk Inhibition
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Hohenester, S.; Kanitz, V.; Kremer, A.E.; Paulusma, C.C.; Wimmer, R.; Kuehn, H.; Denk, G.; Horst, D.; Oude Elferink, R.; Beuers, U. Glycochenodeoxycholate Promotes Liver Fibrosis in Mice with Hepatocellular Cholestasis. Cells 2020, 9, 281. https://doi.org/10.3390/cells9020281
Hohenester S, Kanitz V, Kremer AE, Paulusma CC, Wimmer R, Kuehn H, Denk G, Horst D, Oude Elferink R, Beuers U. Glycochenodeoxycholate Promotes Liver Fibrosis in Mice with Hepatocellular Cholestasis. Cells. 2020; 9(2):281. https://doi.org/10.3390/cells9020281
Chicago/Turabian StyleHohenester, Simon, Veronika Kanitz, Andreas E. Kremer, Coen C. Paulusma, Ralf Wimmer, Helen Kuehn, Gerald Denk, David Horst, Ronald Oude Elferink, and Ulrich Beuers. 2020. "Glycochenodeoxycholate Promotes Liver Fibrosis in Mice with Hepatocellular Cholestasis" Cells 9, no. 2: 281. https://doi.org/10.3390/cells9020281