Activation of Platelet-Derived Growth Factor Receptor Alpha Contributes to Liver Fibrosis

作者：Brian Hayes, Kimberly J. Riehle, Masami Shimizu‐Albergine, Renay L. Bauer, Kelly L. Hudkins, Fredrik Johansson, Matthew M. Yeh, William M. Mahoney, Raymond S. Yeung, Jean S. Campbell · 发表于：PLoS ONE · 年份：2014 · DOI：10.1371/journal.pone.0092925 · 被引用次数：58 · 研究领域：Liver physiology and pathology、Liver Disease Diagnosis and Treatment、Liver Disease and Transplantation

Chronic liver injury leads to fibrosis, cirrhosis, and loss of liver function. Liver cirrhosis is the 12th leading cause of death in the United States, and it is the primary risk factor for developing liver cancer. Fibrosis and cirrhosis result from activation of hepatic stellate cells (HSCs), which are the primary collagen producing cell type in the liver. Here, we show that platelet-derived growth factor receptor α (PDGFRα) is expressed by human HSCs, and PDGFRα expression is elevated in human liver disease. Using a green fluorescent protein (GFP) reporter mouse strain, we evaluated the role of PDGFRα in liver disease in mice and found that mouse HSCs express PDGFRα and expression is upregulated during carbon tetrachloride (CCl4) induced liver injury and fibrosis injection. This fibrotic response is reduced in Pdgfrα heterozygous mice, consistent with the hypothesis that liver fibrosis requires upregulation and activation of PDGFRα. These results indicate that Pdgfrα expression is important in the fibrotic response to liver injury in humans and mice, and suggest that blocking PDGFRα-specific signaling pathways in HSCs may provide therapeutic benefit for patients with chronic liver disease.