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

Journal of Cellular Physiology
Xin Xie, Piergiorgio Percipalle

Abstract

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 TGF-β1 activation and the upregulation of TGF-β target genes. In β-actin null cells, we show evidence that the enhanced TGF-β signaling relies on the active utilization of latent TGF-β1 in the cell culture medium. TGF-β 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 β-actin null cells is inhibited by TGF-β 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 proce...Continue Reading

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Datasets Mentioned

BETA
GSE95830

Methods Mentioned

BETA
protein
Assay
ELISA
Protein Assay
PCR
transfection
FACS
atomic force microscopy

Software Mentioned

Compartment Analysis Bio Application
Ingenuity Pathway Analysis
GraphPad Prism
FlowJo
ImageJ

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