Abstract | OBJECTIVE: DESIGN: RESULTS: pHSCs from F3/F4-scored patients of LF exhibit threefold increased NTCP expressions compared with F0-scored patients (p<0.0001). Sorted-activated HSCs (LX2αSMA+) showed high expressions of NTCP and high TCA uptake in vitro and triggered a further increase in their activations. This phenomenon was inhibited with NTCP small interfering RNA and the NTCP neutralizing antibody. Sorted LX2NTCP+ (high alpha smooth muscle actin (αSMA)/high NTCP) cells showed high phosphorylated pathways of AKT/mTOR and protein kinase C (PKC) accompanied with a decrease in farnesoid X receptor expression. Moreover, LX2NTCP+ cells treated with EGCG, OCA and PKC inhibitor HA-100 significantly decreased NTCP and αSMA. NTCP neutralizing antibody inhibited NTCP (less TCA uptake); it attenuated LF in both CCl4 and Ob/Ob HFD animal models with ameliorated metabolic profile. CONCLUSION: NTCP expression is linearly correlated with fibrosis severity. Modulated BA trafficking could be an important step in LF pathogenesis. Antagonising BA uptake may suggest a therapeutic strategy for preventing disease progression.
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Authors | Ahmad Salhab, Johnny Amer, Yinying Lu, Rifaat Safadi |
Journal | Gut
(Gut)
Vol. 71
Issue 7
Pg. 1373-1385
(07 2022)
ISSN: 1468-3288 [Electronic] England |
PMID | 34266968
(Publication Type: Journal Article)
|
Copyright | © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
Chemical References |
- Antibodies, Neutralizing
- Bile Acids and Salts
- Organic Anion Transporters, Sodium-Dependent
- Peptides
- Symporters
- sodium-bile acid cotransporter
- Taurocholic Acid
- Sodium
|
Topics |
- Animals
- Antibodies, Neutralizing
- Bile Acids and Salts
(metabolism)
- Fibrosis
- Humans
- Liver
(metabolism)
- Liver Cirrhosis
(drug therapy, metabolism)
- Mice
- Organic Anion Transporters, Sodium-Dependent
(genetics)
- Peptides
(metabolism)
- Sodium
(metabolism)
- Symporters
(genetics)
- Taurocholic Acid
(metabolism)
|