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  • Hepatocyte activity of the cholesterol sensor smoothened regulates cholesterol and bile acid homeostasis in mice.

Hepatocyte activity of the cholesterol sensor smoothened regulates cholesterol and bile acid homeostasis in mice.

iScience (2021-09-28)
George D Dalton, Seh-Hoon Oh, Linda Tang, Stephanie Zhang, Amanda L Brown, Venkateshwari Varadharajan, Camelia Baleanu-Gogonea, Valentin Gogonea, Preeti Pathak, J Mark Brown, Anna Mae Diehl
ABSTRACT

Cellular cholesterol is regulated by at least two transcriptional mechanisms involving sterol-regulatory-element-binding proteins (SREBPs) and liver X receptors (LXRs). Although SREBP and LXR pathways are the predominant mechanisms that sense cholesterol in the endoplasmic reticulum and nucleus to alter sterol-regulated gene expression, evidence suggests cholesterol in plasma membrane can be sensed by proteins in the Hedgehog (Hh) pathway which regulate organ self-renewal and are a morphogenic driver during embryonic development. Cholesterol interacts with the G-protein-coupled receptor Smoothened (Smo), which impacts downstream Hh signaling. Although evidence suggests cholesterol influences Hh signaling, it is not known whether Smo-dependent sterol sensing impacts cholesterol homeostasis in vivo. We examined dietary-cholesterol-induced reorganization of whole-body sterol and bile acid (BA) homeostasis in adult mice with inducible hepatocyte-specific Smo deletion. These studies demonstrate Smo in hepatocytes plays a regulatory role in sensing and feedback regulation of cholesterol balance driven by excess dietary cholesterol.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Cyp7a1 Antibody, clone 15B9.1, clone 15B9.1, from mouse
Rabbit IgG HRP Linked Whole Ab, Cytiva NA934-1ML
Sigma-Aldrich
RIPA Buffer