Tartrate-resistant acid phosphatase 5 promotes pulmonary fibrosis by modulating β-catenin signaling

Yinan Hu, Qi Wang, Jun Yu, Qing Zhou, Yanhan Deng, Juan Liu, Lei Zhang, Yongjian Xu, Weining Xiong () and Yi Wang ()
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Yinan Hu: Huazhong University of Science and Technology
Qi Wang: Huazhong University of Science and Technology
Jun Yu: Huazhong University of Science and Technology
Qing Zhou: Huazhong University of Science and Technology
Yanhan Deng: Huazhong University of Science and Technology
Juan Liu: Huazhong University of Science and Technology
Lei Zhang: Huazhong University of Science and Technology
Yongjian Xu: Huazhong University of Science and Technology
Weining Xiong: Huazhong University of Science and Technology
Yi Wang: Huazhong University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options. Tartrate-resistant acid phosphatase 5 (ACP5) performs a variety of functions. However, its role in IPF remains unclear. Here, we demonstrate that the levels of ACP5 are increased in IPF patient samples and mice with bleomycin (BLM)-induced pulmonary fibrosis. In particular, higher levels of ACP5 are present in the sera of IPF patients with a diffusing capacity of the lungs for carbonmonoxide (DLCO) less than 40% of the predicted value. Additionally, Acp5 deficiency protects mice from BLM-induced lung injury and fibrosis coupled with a significant reduction of fibroblast differentiation and proliferation. Mechanistic studies reveal that Acp5 is upregulated by transforming growth factor-β1 (TGF-β1) in a TGF-β receptor 1 (TGFβR1)/Smad family member 3 (Smad3)-dependent manner, after which Acp5 dephosphorylates p-β-catenin at serine 33 and threonine 41, inhibiting the degradation of β-catenin and subsequently enhancing β-catenin signaling in the nucleus, which promotes the differentiation, proliferation and migration of fibroblast. More importantly, the treatment of mice with Acp5 siRNA-loaded liposomes or Acp5 inhibitor reverses established lung fibrosis. In conclusions, Acp5 is involved in the initiation and progression of pulmonary fibrosis and strategies aimed at silencing or suppressing Acp5 could be considered as potential therapeutic approaches against pulmonary fibrosis.

Date: 2022
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DOI: 10.1038/s41467-021-27684-9

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