What question did this study set out to answer?

This research aims to understand how PADI2-mediated citrullination contributes to pulmonary fibrosis and inflammation in silicosis.

March 10, 2026Open Access

Inhibition of PADI2-mediated vimentin citrullination alleviates silica-induced pulmonary fibrosis in mice

FJFuyu Jin YLYaqian LiShanxi Agricultural University TLTian LiNorth China University of Science and Technology

Key Points

This research aims to understand how PADI2-mediated citrullination contributes to pulmonary fibrosis and inflammation in silicosis.
Examined citrullinated proteomic profiles in mice and macrophages exposed to silica
Analyzed the effects of Cit-Vim on cytokine production and TLR4 signaling
Utilized RNA sequencing to identify EGR1 as a target of PADI2
Performed pharmacological inhibition and genetic knockout of PADI2 to assess lung inflammation
Silicotic mice showed elevated levels of Cit-Vim and citrullinated peptides
Cit-Vim increased TNF-α, IL-6, and IL-1β production in silica-treated macrophages
EGR1 was identified as a mediator in the inflammatory response
Inhibition or knockout of PADI2 reduced lung inflammation and fibrosis

Abstract

Silicosis remains a critical occupational health concern worldwide, lacking effective treatments due to unclear mechanisms. In this study, we investigated the citrullinated proteomic profile and its effects in mice exposed to silica. Our findings demonstrated elevated levels of citrullinated peptides and citrullinated vimentin (Cit-Vim) in silicotic mice and silica-treated macrophages, regulated by peptidylarginine deiminase (PADI2). Unlike vimentin, Cit-Vim amplified the production of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and IL-1β in silica-treated macrophages through interaction with Toll-like receptor 4 (TLR4) signaling. RNA sequencing revealed that early growth response protein 1 (EGR1) is a target of PADI2, with Cit-Vim inducing lung inflammation via EGR1 signaling. Pharmacological inhibition or genetic knockout of Padi2 attenuated silica-induced lung inflammation and fibrosis. These findings suggest that targeting PADI2 may represent a novel therapeutic strategy of silicosis.

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