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Elevated transforming growth factor ? signaling activation in ?-actin-knockout mouse embryonic fibroblasts enhances myofibroblast features.


ABSTRACT: Signaling by the transforming growth factor-? (TGF-?) is an essential pathway regulating a variety of cellular events. TGF-? is produced as a latent protein complex and is required to be activated before activating the receptor. The mechanical force at the cell surface is believed to be a mechanism for latent TGF-? activation. Using ?-actin null mouse embryonic fibroblasts as a model, in which actin cytoskeleton and cell-surface biophysical features are dramatically altered, we reveal increased TGF-?1 activation and the upregulation of TGF-? target genes. In ?-actin null cells, we show evidence that the enhanced TGF-? signaling relies on the active utilization of latent TGF-?1 in the cell culture medium. TGF-? signaling activation contributes to the elevated reactive oxygen species production, which is likely mediated by the upregulation of Nox4. The previously observed myofibroblast phenotype of ?-actin null cells is inhibited by TGF-? signaling inhibition, while the expression of actin cytoskeleton genes and angiogenic phenotype are not affected. Together, our study shows a scenario that the alteration of the actin cytoskeleton and the consequent changes in cellular biophysical features lead to changes in cell signaling process such as TGF-? activation, which in turn contributes to the enhanced myofibroblast phenotype.

SUBMITTER: Xie X 

PROVIDER: S-EPMC6220129 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Elevated transforming growth factor β signaling activation in β-actin-knockout mouse embryonic fibroblasts enhances myofibroblast features.

Xie Xin X   Percipalle Piergiorgio P  

Journal of cellular physiology 20180531 11


Signaling by the transforming growth factor-β (TGF-β) is an essential pathway regulating a variety of cellular events. TGF-β is produced as a latent protein complex and is required to be activated before activating the receptor. The mechanical force at the cell surface is believed to be a mechanism for latent TGF-β activation. Using β-actin null mouse embryonic fibroblasts as a model, in which actin cytoskeleton and cell-surface biophysical features are dramatically altered, we reveal increased  ...[more]

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