The long noncoding RNA, p53-induced long noncoding RNA TP53 target 1 (TP53TG1), is a major suppressor of fibroblast activation in idiopathic pulmonary fibrosis (IPF), a new study published in Cell Death & Disease found. It could therefore be targeted as a treatment for the disease.
It is known that long noncoding RNAs are crucial for the regulation of cellular homeostasis. However, their exact role in IPF is not well understood.
In the present study, a team of researchers from China found that a particular long noncoding RNA, TP53TG1, was dysregulated in IPF.
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Through functional experiments, the researchers found that the overexpression of TP53TG1 attenuated the increased expression of fibronectin 1, collagen 1α1, collagen 3α1, and actin α2 messenger RNA. It also attenuated the increased expression of fibronectin 1 and collagen I at the protein level. Finally, it reduced the excessive proliferation, migration, and differentiation of mouse and human lung fibroblasts.
The team also conducted some in vivo experiments and showed that the forced expression of TP53TG1 using an adeno-associated virus 5 vector prevented bleomycin-induced fibrosis in mice. It also reversed the lung fibrosis that was already established.
“Mechanistically, TP53TG1 was found to bind to . . . tight junction proteins,” the researchers wrote. “Importantly, we found that TP53TG1 binds to the Myosin Heavy Chain 9 (MYH9) to inhibit its protein expression and thus the MYH9-mediated activation of fibroblasts.”
Long noncoding RNAs are RNA molecules that are usually longer than 200 nucleotides and lack the potential to code for any protein. Research has shown that they are widely expressed and play key roles in the regulation of gene expression. They have also been shown to be involved in the pathophysiology of IPF by activating fibroblasts.
Sun J, Guo Y, Chen T, et al. Systematic analyses identify the anti-fibrotic role of lncRNA TP53TG1 in IPF. Cell Death Dis. 2022;13(6):525. doi:10.1038/s41419-022-04975-7