Differential gene expression in periportal and perivenous mouse hepatocytes

TLDR

Hepatocytes in the periportal and perivenous zones of the liver lobule differ markedly in enzyme and protein levels and activities. The study aimed to map global gene expression differences between periportal and perivenous hepatocytes. Periportal and perivenous hepatocytes were isolated by collagenase/digitonin perfusion, subjected to microarray analysis, and a subset of 20 genes was validated by real‑time RT‑PCR. Microarray identified 198 genes with ≥2‑fold differential expression, including key enzymes of glycolysis, gluconeogenesis, fatty‑acid, cholesterol, bile‑acid, amino‑acid metabolism, and xenobiotic phase I/II pathways, confirming and extending known metabolic zonation at the transcriptional level.

Abstract

Hepatocytes located in the periportal and perivenous zones of the liver lobule show remarkable differences in the levels and activities of various enzymes and other proteins. To analyze global gene expression patterns of periportal and perivenous hepatocytes, enriched populations of the two cell types were isolated by combined collagenase/digitonin perfusion from mouse liver and used for microarray analysis. In total, 198 genes and expressed sequences were identified that demonstrated a ≥ 2‐fold difference in expression between hepatocytes from the two different zones of the liver. A subset of 20 genes was additionally analyzed by real‐time RT‐PCR, validating the results obtained by the microarray analysis. Several of the differentially expressed genes encoded key enzymes of intermediary metabolism, including those involved in glycolysis and gluconeogenesis, fatty acid degradation, cholesterol and bile acid metabolism, amino acid degradation and ammonia utilization. In addition, several enzymes of phase I and phase II of xenobiotic metabolism were differentially expressed in periportal and perivenous hepatocytes. Our results confirm previous findings on metabolic zonation in liver, and extend our knowledge of the regulatory mechanisms at the transcriptional level.