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Phf14, a novel regulator of mesenchyme growth via platelet-derived growth factor (PDGF) receptor-?.


ABSTRACT: The regulation of mesenchymal cell growth by signaling molecules plays an important role in maintaining tissue functions. Aberrant mesenchymal cell proliferation caused by disruption of this regulatory process leads to pathogenetic events such as fibrosis. In the current study we have identified a novel nuclear factor, Phf14, which controls the proliferation of mesenchymal cells by regulating PDGFR? expression. Phf14-null mice died just after birth due to respiratory failure. Histological analyses of the lungs of these mice showed interstitial hyperplasia with an increased number of PDGFR?(+) mesenchymal cells. PDGFR? expression was elevated in Phf14-null mesenchymal fibroblasts, resulting in increased proliferation. We demonstrated that Phf14 acts as a transcription factor that directly represses PDGFR? expression. Based on these results, we used an antibody against PDGFR? to successfully treat mouse lung fibrosis. This study shows that Phf14 acts as a negative regulator of PDGFR? expression in mesenchymal cells undergoing normal and abnormal proliferation, and is a potential target for new treatments of lung fibrosis.

SUBMITTER: Kitagawa M 

PROVIDER: S-EPMC3431629 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Phf14, a novel regulator of mesenchyme growth via platelet-derived growth factor (PDGF) receptor-α.

Kitagawa Michinori M   Takebe Atsushi A   Ono Yuichi Y   Imai Toshio T   Nakao Kazuki K   Nishikawa Shin-Ichi S   Era Takumi T  

The Journal of biological chemistry 20120623 33


The regulation of mesenchymal cell growth by signaling molecules plays an important role in maintaining tissue functions. Aberrant mesenchymal cell proliferation caused by disruption of this regulatory process leads to pathogenetic events such as fibrosis. In the current study we have identified a novel nuclear factor, Phf14, which controls the proliferation of mesenchymal cells by regulating PDGFRα expression. Phf14-null mice died just after birth due to respiratory failure. Histological analys  ...[more]

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