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Novel murine model of hepatocyte‐specific human platelet‐derived growth factor alpha expression (649.9)
Author(s) -
Kikuchi Alexander,
Lee Jung Min,
Monga Satdarshan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.649.9
Subject(s) - platelet derived growth factor receptor , downregulation and upregulation , platelet derived growth factor , cancer research , fibrosis , growth factor , myofibroblast , hepatocyte , genetically modified mouse , growth factor receptor , biology , liver injury , hepatocyte growth factor , hepatic stellate cell , immunology , medicine , pathology , microbiology and biotechnology , endocrinology , transgene , receptor , signal transduction , in vitro , biochemistry , gene
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 overt phenotype. In conjunction with previously described human and mouse‐specific monoclonal anti‐PDGFRα antibodies, this mouse strain will allow the investigation of a cell‐specific role of PDGFRα in experimental models of chronic liver injury and regeneration. Grant Funding Source : T32: HL094295 ANGIOPATHY TRAINING GRANT; R01: DK095498 ROLE OF PDGFRALPHA IN LIVER PATHO‐BIOLOGY