Hypoxia upregulates Cxcl12 in hepatocytes by a complex mechanism involving hypoxia-inducible factors and transforming growth factor-β.

ABSTRACT:

Introduction

Cxcl12, or stromal-derived factor-1, is a chemokine produced by several hepatic cell types, including hepatocytes, after liver injury and surgical resection. Studies have revealed that Cxcl12 is important for regeneration of the liver after surgical resection and for development of liver fibrosis during chronic liver injury. While the function of Cxcl12 in the liver is well established, the mechanism by which Cxcl12 is upregulated is not fully understood. Because regions of hypoxia develop in the liver following injury, we tested the hypothesis that hypoxia upregulates Cxcl12 in hepatocytes by a hypoxia-inducible factor (HIF)-dependent mechanism.

Methods

To test this hypothesis, primary mouse hepatocytes were isolated from the livers of HIF-1α-deficient mice or

SUBMITTER: Strickland J 

PROVIDER: S-EPMC7255688 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature