# Expression of Selected Pharmacologically Relevant Transporters in Murine Non-Parenchymal Liver Cells Compared to Hepatocytes

## TL;DR

The study compares transporter expression in mouse liver non-parenchymal cells and hepatocytes, finding that NPCs have higher levels of certain drug transporters.

## Contribution

The study identifies specific transporters in non-parenchymal liver cells that may be important for drug transport and preclinical testing.

## Key findings

- NPCs show higher expression of Abcc1/Mrp1, Abcc5/Mrp5, and other transporters compared to hepatocytes.
- Hepatocytes predominantly express Abcc2/Mrp2, Abcg2/Bcrp, and Slc22a1/Oct1.
- Kupffer and endothelial cells show minimal differences in transporter expression.

## Abstract

Primary hepatocytes are widely used in preclinical drug development, with their transporter expression being well-characterized. However, less is known about non-parenchymal liver cells (NPCs), which constitute 40% of the liver’s cell population and include sinusoidal endothelial cells and Kupffer cells. This study aimed to characterize transporter expression in murine NPCs compared to hepatocytes. Cell fractions were isolated using collagenase perfusion, density gradient centrifugation, and magnetic-activated cell sorting (MACS) with F4/80 and CD146 antibodies. Transporter expression and separation quality were analyzed via RT-qPCR. Results showed NPC-specific genes were significantly lower in hepatocytes and vice versa. Importantly, NPCs exhibited higher expression of several transporters: Abcc1/Mrp1 (87-fold), Abcc4/Mrp4 (4-fold), Abcc5/Mrp5 (40-fold), as well as Slc15a2/PepT2 (16-fold), Slc28a2/Cnt2 (20-fold), Slco3a1/Oatp3a1 (15-fold), and Slco4a1/Oatp4a1 (13-fold), compared to hepatocytes. Hepatocytes showed dominant expression of Abcc2/Mrp2, Abcg2/Bcrp, Slc22a1/Oct1, and others. Minimal differences in transporter expression were found between Kupffer and endothelial cells. In conclusion, the efflux transporters Abcc1/Mrp1 and Abcc5/Mrp5 are predominantly expressed in NPCs. This suggests that NPCs are potentially relevant for the transport of certain drugs and should be included in in vitro preclinical testing.