LRRC8A Protein and Its Role in Ion Channel Regulation and Bile Formation

June 10, 2022

A research team from the Feranchak Laboratory in the Division of Pediatric Gastroenterology, Hepatology and Nutrition at UPMC Children’s Hospital of Pittsburgh published new findings in the journal Hepatology on the role of a specific ion channel in liver cells that contributes to biliary secretion and bile formation.

Senior staff researcher Nikolay A. Shcheynikov, PhD, was the lead author of the study. Andrew Feranchak MD, chief of the Division of Pediatric Gastroenterology at UPMC Children’s was the study’s senior author. Also collaborating on the study from the Feranchak Laboratory was Kristy Boggs, PhD, research assistant professor, and Anthony Green, PhD, from the UPMC Hillman Cancer Center Tissue and Pathology Core.

In 2014, the leucine-rich repeat-containing protein 8, subfamily a (LRRC8A) protein was discovered and found to regulate chloride ion transport in epithelial cells as a response to volume changes within cells. The new study from the Feranchak Laboratory team sought to determine if LRRC8A functioned within biliary epithelial cells, cells largely responsible for bile secretion in the liver, the dysfunction of which can lead to various cholestatic liver disorders. Dr. Feranchak’s laboratory is primarily interested in the cellular and molecular mechanisms of hepatobiliary transport and cholestatic liver disease that arise from dysfunction of these mechanisms.

Their new study, performed in both small and large mouse cholangiocytes, demonstrates that this channel is an important contributor to liver bile formation and cell volume regulation. This finding may point toward LRRC8A as being a potential therapeutic target for treating cholestatic liver diseases or those liver diseases in which bile formation is impaired.

Learn more about the Feranchak Laboratory.

Reference

Shcheynikov N, Boggs K, Green A, Feranchak AP. Identification of the Chloride Channel, Leucine-rich Repeat-containing Protein 8, Subfamily a (LRRC8A), in Mouse Cholangiocytes. Hepatology. 2022 April 21. Online ahead of print.