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<p>Bile acids (BAs) synthesized from cholesterol in the liver play a crucial role in the absorption of fat-soluble vitamins and cholesterol in the small intestine. Hepatocytes possess basolateral uptake transporters, such as Na + /taurocholate cotransporting polypeptide (NTCP) and organic anion transporting polypeptide (OATPs), which facilitate the uptake of bile salts from portal blood. Efflux transporters, including bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2), mediate the canalicular excretion of biliary constituents, a rate-limiting step in bile secretion. This review explores the roles of hepatobiliary transporters and their regulatory nuclear receptors in BA homeostasis, focusing on their clinical and therapeutic implications. Alternative basolateral efflux systems (MRP3, MRP1, MRP4, and OSTα-OSTβ) and hepatic canalicular export systems (BSEP, MRP2, MDR3, and MDR1) are discussed in the context of bile formation and drug transport. Gallstone pathogenesis is linked to canalicular transporters for phosphatidylcholine (MDR3), cholesterol (ABCG5/8), and BAs (BSEP), as well as their regulating nuclear receptors. Understanding the complex interplay between hepatobiliary transporters and nuclear receptors in BA homeostasis is essential for developing novel therapeutic strategies for cholestatic liver diseases and gallstone formation.</p>

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The Role of Hepatobiliary Transporters in Bile Acid Homeostasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月12日

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  • Thamer Abdulla Mohammed,
  • Munaf H. Zalzala

摘要

Bile acids (BAs) synthesized from cholesterol in the liver play a crucial role in the absorption of fat-soluble vitamins and cholesterol in the small intestine. Hepatocytes possess basolateral uptake transporters, such as Na + /taurocholate cotransporting polypeptide (NTCP) and organic anion transporting polypeptide (OATPs), which facilitate the uptake of bile salts from portal blood. Efflux transporters, including bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2), mediate the canalicular excretion of biliary constituents, a rate-limiting step in bile secretion. This review explores the roles of hepatobiliary transporters and their regulatory nuclear receptors in BA homeostasis, focusing on their clinical and therapeutic implications. Alternative basolateral efflux systems (MRP3, MRP1, MRP4, and OSTα-OSTβ) and hepatic canalicular export systems (BSEP, MRP2, MDR3, and MDR1) are discussed in the context of bile formation and drug transport. Gallstone pathogenesis is linked to canalicular transporters for phosphatidylcholine (MDR3), cholesterol (ABCG5/8), and BAs (BSEP), as well as their regulating nuclear receptors. Understanding the complex interplay between hepatobiliary transporters and nuclear receptors in BA homeostasis is essential for developing novel therapeutic strategies for cholestatic liver diseases and gallstone formation.