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In the referenced article, Figure 1 is incorrect. The corrected figure is shown below, with the labels BA, FGFR4, OATP1, FXR, MRP3, and ASBT added to it.
FIG 1.
BA synthesis and transport pathway. BAs are taken up by NTCP, OST‐α, and OST‐β on the hepatocyte basolateral membrane, as well as synthesized from cholesterol by CYP7A1, followed by transport into canaliculi by the BSEP. Other constituents of bile include phosphatidylcholine, transported by canalicular MDR3, and phosphatidylserine, shuttled by canalicular ATP8B1. The TJP2 maintains the canalicular membrane and inhibits the reflux of BA back into the hepatocyte. The master regulator of BA metabolism is FXR, which is induced by BA and activates SHP, leading to inhibition of both NTCP transport of BA into the hepatocyte and CYP7A1‐induced synthesis of BA, and stimulates BSEP export of BA. The protein defects associated with the various PFIC types are highlighted with a black outline. (Not shown is MYO5B, which interacts with RAB11A, altering the targeting of BSEP to the canalicular membrane.) Approximately 95% of Bas are taken up by the ASBT on the ileal enterocyte and enter the portal circulation through enterocyte transporters OST‐α, OST‐β, and MRP3, resulting in enterohepatic recirculation of BAs. BAs also induce enterocyte FXR, leading to FGF19/FGFR4 activation with downstream inhibition of CYP7A1‐induced BA synthesis. Adapted with permission from Nature Reviews Gastroenterology & Hepatology.1 Copyright 2019, Springer Nature Publishing AG. Abbreviation: PS, phosphatidylserine.