SPP1 promotes the polarization of M2 macrophages through the Jak2/Stat3 signaling pathway and accelerates the progression of idiopathic pulmonary fibrosis

Yang,Xuelian; Liu,Ziqin; Zhou,Jiawei; Guo,Jianqiang; Han,Tao; Liu,Yafeng; Li,Yunyun; Bai,Ying; Xing,Yingru; Wu,Jing; Hu,Dong

doi:10.3892/ijmm.2024.5413

SPP1 promotes the polarization of M2 macrophages through the Jak2/Stat3 signaling pathway and accelerates the progression of idiopathic pulmonary fibrosis

Authors:
- Xuelian Yang
- Ziqin Liu
- Jiawei Zhou
- Jianqiang Guo
- Tao Han
- Yafeng Liu
- Yunyun Li
- Ying Bai
- Yingru Xing
- Jing Wu
- Dong Hu
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Affiliations: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China, Department of Clinical Laboratory, Anhui Zhongke Gengjiu Hospital, Hefei, Anhui 230000, P.R. China
Published online on: August 8, 2024 https://doi.org/10.3892/ijmm.2024.5413
Article Number: 89
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease that requires further investigation to understand its pathogenesis. The present study demonstrated that secreted phosphoprotein 1 (SPP1) was aberrantly highly expressed in the lung tissue of patients with IPF and was significantly positively associated with macrophage and T‑cell activity. Cell localization studies revealed that SPP1 was primarily overexpressed in macrophages, rather than in T cells. Functionally, knocking down SPP1 expression in vitro inhibited the secretion of fibrosis‑related factors and M2 polarization in macrophages. Furthermore, knocking down SPP1 expression inhibited the macrophage‑induced epithelial‑to‑mesenchymal transition in both epithelial and fibroblastic cells. Treatment with SPP1 inhibitors in vivo enhanced lung function and ameliorated pulmonary fibrosis. Mechanistically, SPP1 appears to promote macrophage M2 polarization by regulating the JAK/STAT3 signaling pathway both in vitro and in vivo. In summary, the present study found that SPP1 promotes M2 polarization of macrophages through the JAK2/STAT3 signaling pathway, thereby accelerating the progression of IPF. Inhibition of SPP1 expression in vivo can effectively alleviate the development of IPF, indicating that SPP1 in macrophages may be a potential therapeutic target for IPF.

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