Peroxiredoxin 4 in alveolar macrophages: a novel target for the treatment of silicosis fibrosis

Author:

Zhou Jiawei1,Bai Ying1,Guo Jianqiang1,Liu Yafeng1,Zhang Xin1,Liang Chao1,Wang Wenyang1,Xing Yingru1,Wu Jing1,Hu Dong1

Affiliation:

1. Anhui University of Science and Technology

Abstract

Abstract Silicosis is an occupational disease with the highest morbidity and mortality, and no specific medicine or recognized cure is available. Here, for the first time, we identified peroxiredoxin 4 (PRDX4) as a tissue-specific regulator of alveolar macrophages (AMs) in silicosis patients. We construct mouse models of early silicosis with self-repair and silicosis with systemic inhibition or conditional knockdown of PRDX4. Mechanistically, PRDX4 is selectively and highly expressed in AMs of silicosis patients and mice, which activates AMs through AKT/NF-κB pathway, thus promoting the transformation of pulmonary epithelial cells and fibroblasts. Functionally, systemic administration of a PRDX4 inhibitor (Conoidin A) significantly improves pulmonary self-repair in early silicosis mice. Interestingly, when knocking down PRDX4 of AMs by AAV virus vector, it not only prominently prevents the progression of crystalline silica (CS)-induced pulmonary fibrosis in mice, but also exhibits lower side effects. Taken together, these findings highlight PRDX4 as a novel target of AMs in regulating pulmonary inflammation and fibrosis, and targeted inhibition of PRDX4 in AMs may support a potential therapeutic strategy for silicosis.

Publisher

Research Square Platform LLC

Reference37 articles.

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