Lung fibrosis is challenging to treat and largely irreversible. There have been signs that clearance of senescent cells can improve the condition, but this has yet to move beyond early human safety trials. Here researchers take a more traditional approach to assessing and then tinkering with the expression of specific genes to produce a reduction in fibrosis in animal models. After finding that ID1 and ID3 exhibited elevated expression in some lung cells, they showed that reducing expression via a variety of means caused some degree of reversal of fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive disease in which scar tissue builds up in the lungs, making it increasingly difficult to breathe. Existing therapies can slow disease progression but do not stop or reverse it, and most patients survive only three to five years after diagnosis. The research combined analyses of human lung tissue and cells from patients with IPF with several experimental models in mice. The team found that ID1 and ID3 levels are elevated in diseased lung fibroblasts - cells that drive the formation of scar tissue.
When both proteins were inhibited, fibroblast activation was significantly reduced, limiting the processes that lead to pulmonary fibrosis. The researchers tested multiple strategies to block ID1 and ID3, including a small molecule drug and a targeted gene therapy approach. Across these approaches, inhibition of the proteins not only slowed disease progression but also reduced established pulmonary fibrosis in mice and improved lung function. The study also sheds light on how these proteins contribute to disease. ID1 and ID3 regulate fibroblast growth through cell cycle pathways and promote scarring through MEK/ERK signaling - key mechanisms underlying pulmonary fibrosis.
Link: https://www.eurekalert.org/news-releases/1125917
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