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PDGFRα in Liver Development & Regeneration
Author(s) -
Awuah Prince,
NejakBowen Kari,
Misse Amalea,
Singh Sucha,
Monga Satdarshan P
Publication year - 2011
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.25.1_supplement.115.4
Subject(s) - platelet derived growth factor receptor , liver regeneration , biology , hepatocyte , platelet derived growth factor , phenotype , cell growth , immunohistochemistry , regeneration (biology) , growth factor , endocrinology , medicine , andrology , cancer research , receptor , microbiology and biotechnology , immunology , gene , genetics , in vitro
Platelet derived growth factor Receptor‐α (PDGFRα) signaling is indispensable during development. Global inactivation of PDGFRα is embryonic lethal. Here we examine expression and role of PDGFRα in liver biology. Robust PDGFRα expression was detected only at early stages of liver development. Using phosphospecific antibodies to PDGFRα, temporal phosphorylation events were identified during hepatic development indicating downstream activation of specific pathways. Adult hepatocytes expressed only low levels of PDGFRα. To determine its role in adult liver, we generated conditional PDGFRα knockouts (KO) by breeding floxed PDGFRα and albumin‐cre recombinase mice. A significant decrease in PDGFRα expression was evident in KO at 2 months. However, KO did not exhibit any overt phenotype and livers showed normal hepatocyte morphology, survival and proliferation. Serum biochemistry also revealed normal hepatic functions. To further dissect any role of PDGFRα in hepatocyte proliferation and survival, we examined liver regeneration in KO and control mice after partial‐hepatectomy (Phx). We identified an increase in total PDGFRα expression at 24hrs after Phx in control mice. KO mice showed significantly lower PDGFRα levels at 24hrs although they did exhibit some increase over baseline. Absence of PDGFRα did not lead to any changes in hepatocyte proliferation or survival at 24hrs or 48hrs after Phx in KO as indicated by PCNA and TUNEL immunohistochemistry, respectively. Thus, we report the generation of a liver‐specific PDGFRα KO mouse that lacks any overt phenotype. However, increased expression of PDGFRα during hepatic development and during regeneration is evident and will need further evaluation.