Novel murine model of hepatocyte-specific human platelet-derived growth factor alpha expression (649.9)

Hepatic fibrosis is a common outcome of chronic liver disease from many etiologies and represents a potentially reversible stage of disease progression. Hepatocytes play an important role in this pathologic process through apoptosis, and release of cytokines and growth factors to influence myofibroblast activation and altered proliferation. We have found elevated hepatocyte platelet-derived growth factor α (PDGFRα) expression in experimental fibrosis and in patients with fibrosis, as well as reduced injury in PDGFRα-conditional knockout mice. While these findings suggest that PDGFRα upregulation may be involved in hepatic injury, it remains undetermined whether PDGFRα upregulation in hepatocytes plays a compensatory or pathological role. To address this question, we have generated a novel transgenic mouse model expressing human PDGFRA in hepatocytes under the control of an albumin-promoter. We show that this animal expresses human PDGFRα in whole liver lysates, and overexpresses total PDGFRα but lacks an ...