Priyanshi Patel ’22

Idiopathic Pulmonary Fibrosis (IPF) is an irreversible, chronic, and lethal disease of unknown etiology. IPF is characterized by excessive deposition of extracellular matrix (ECM), which is secreted mainly by activated fibroblasts under certain stimuli. Recent studies have evaluated alterations with DNA methylation as a collective driver of IPF. Few studies explore global DNA methylation in lung fibrosis, but none focused on transforming growth factor-beta (TGF-β1) as being a modifier of the DNA methylome. Scientists from the National Institute of Respiratory Diseases and the University of Sciences in Mexico sought to analyze changes in methylation and gene transcription in normal and IPF fibroblasts following TGF-β1 treatment. 

Transforming growth factor-beta (TGF-β1) is a potent mediator of tissue remodeling and fibrosis. It promotes fibroblast proliferation and produces multiple components that increase contractility and apoptosis resistance. The effects of TGF-β1 were analyzed on primary fibroblasts derived from normal and IPF lungs, which were obtained through open lung biopsy. TGF-β1 induced numerous gene expression changes after a short-term treatment in normal fibroblasts. Greater methylation changes were observed after long periods of simulation, mainly in IPF fibroblasts. DNA methyltransferase 3 alpha (DNMT3a) and tet methylcytosine dioxygenase 3 (TET3), which are important elements for DNA methylation and demethylation, were affected by TGF-β1 on DNA methylation in lung fibroblasts. 

This study examined, for the first time, the effect of TGF-β1 on DNA methylation in lung fibroblasts. It also affected important elements such as DNMT3a and TET3 and noted that IPF and normal lung derived fibroblasts responded differently due to prior exposure to the fibrotic environment within the lungs. This study was important because it evaluated how TGF-β1 could modify DNA methylome and demonstrated that TGF-β1 could induce upregulation of DNMT3a and TET3 expression, along with profound changes in DNA methylation patterns on fibroblasts.

References: 

1. M. Negreros, et. al., Transforming growth factor beta 1 induces methylation changes in lung fibroblasts. Public Library of Science One 14, 1-13 (2019). doi: 10.1371/journal.pone.0223512
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