Zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment.

The transcription factor Zfp148 (Zbp-89, BFCOL, BERF1, htβ) interacts physically with the tumor suppressor p53 and is implicated in cell cycle control, but the physiological role of Zfp148 remains unknown. Here we show that Zfp148 deficiency leads to respiratory distress and lethality in newborn mic...

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Main Authors: Volkan I Sayin, Anna Nilton, Mohamed X Ibrahim, Pia Ågren, Erik Larsson, Marleen M Petit, Lillemor Mattsson Hultén, Marcus Ståhlman, Bengt R Johansson, Martin O Bergo, Per Lindahl
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3566028?pdf=render
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spelling doaj-93f7a0c3f0cf4aa9948ba42e4716e5d72020-11-25T01:29:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5572010.1371/journal.pone.0055720Zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment.Volkan I SayinAnna NiltonMohamed X IbrahimPia ÅgrenErik LarssonMarleen M PetitLillemor Mattsson HulténMarcus StåhlmanBengt R JohanssonMartin O BergoPer LindahlThe transcription factor Zfp148 (Zbp-89, BFCOL, BERF1, htβ) interacts physically with the tumor suppressor p53 and is implicated in cell cycle control, but the physiological role of Zfp148 remains unknown. Here we show that Zfp148 deficiency leads to respiratory distress and lethality in newborn mice. Zfp148 deficiency prevented structural maturation of the prenatal lung without affecting type II cell differentiation or surfactant production. BrdU analyses revealed that Zfp148 deficiency caused proliferation arrest of pulmonary cells at E18.5-19.5. Similarly, Zfp148-deficient fibroblasts exhibited proliferative arrest that was dependent on p53, raising the possibility that cell stress is part of the underlying mechanism. Indeed, Zfp148 deficiency lowered the threshold for activation of p53 under oxidative conditions. Moreover, both in vivo and cellular phenotypes were rescued on Trp53(+/-) or Trp53(-/-) backgrounds and by antioxidant treatment. Thus, Zfp148 prevents respiratory distress and lethality in newborn mice by attenuating oxidative stress-dependent p53-activity during the saccular stage of lung development. Our results establish Zfp148 as a novel player in mammalian lung maturation and demonstrate that Zfp148 is critical for cell cycle progression in vivo.http://europepmc.org/articles/PMC3566028?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Volkan I Sayin
Anna Nilton
Mohamed X Ibrahim
Pia Ågren
Erik Larsson
Marleen M Petit
Lillemor Mattsson Hultén
Marcus Ståhlman
Bengt R Johansson
Martin O Bergo
Per Lindahl
spellingShingle Volkan I Sayin
Anna Nilton
Mohamed X Ibrahim
Pia Ågren
Erik Larsson
Marleen M Petit
Lillemor Mattsson Hultén
Marcus Ståhlman
Bengt R Johansson
Martin O Bergo
Per Lindahl
Zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment.
PLoS ONE
author_facet Volkan I Sayin
Anna Nilton
Mohamed X Ibrahim
Pia Ågren
Erik Larsson
Marleen M Petit
Lillemor Mattsson Hultén
Marcus Ståhlman
Bengt R Johansson
Martin O Bergo
Per Lindahl
author_sort Volkan I Sayin
title Zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment.
title_short Zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment.
title_full Zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment.
title_fullStr Zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment.
title_full_unstemmed Zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment.
title_sort zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description The transcription factor Zfp148 (Zbp-89, BFCOL, BERF1, htβ) interacts physically with the tumor suppressor p53 and is implicated in cell cycle control, but the physiological role of Zfp148 remains unknown. Here we show that Zfp148 deficiency leads to respiratory distress and lethality in newborn mice. Zfp148 deficiency prevented structural maturation of the prenatal lung without affecting type II cell differentiation or surfactant production. BrdU analyses revealed that Zfp148 deficiency caused proliferation arrest of pulmonary cells at E18.5-19.5. Similarly, Zfp148-deficient fibroblasts exhibited proliferative arrest that was dependent on p53, raising the possibility that cell stress is part of the underlying mechanism. Indeed, Zfp148 deficiency lowered the threshold for activation of p53 under oxidative conditions. Moreover, both in vivo and cellular phenotypes were rescued on Trp53(+/-) or Trp53(-/-) backgrounds and by antioxidant treatment. Thus, Zfp148 prevents respiratory distress and lethality in newborn mice by attenuating oxidative stress-dependent p53-activity during the saccular stage of lung development. Our results establish Zfp148 as a novel player in mammalian lung maturation and demonstrate that Zfp148 is critical for cell cycle progression in vivo.
url http://europepmc.org/articles/PMC3566028?pdf=render
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