2. Academic Validation
  3. BI-2536 attenuates IPF progression by inhibiting the PLK2/JNK/SP1 Signaling pathway in AT2 cells

BI-2536 attenuates IPF progression by inhibiting the PLK2/JNK/SP1 Signaling pathway in AT2 cells

  • Int Immunopharmacol. 2026 Jan 1;168(Pt 1):115812. doi: 10.1016/j.intimp.2025.115812.
Anqi Cheng 1,  Jiawei Zhou 2,  Jianqiang Guo 3,  Tianxiang Qi 4,  Ying Bai 5,  Dong Hu 6,  Jing Wu 7
Affiliations

Affiliations

  • 1 School of Medicine, Anhui University of Science and Technology, Huainan 232000, Anhui, China,; Anhui Occupational Health and Safety Engineering Laboratory, Huainan 232000, Anhui, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, AUST, Huainan 232000, Anhui, China.
  • 2 Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, AUST, Huainan 232000, Anhui, China; Key Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and Technology, Huainan 232000, Anhui, China.
  • 3 School of Medicine, Anhui University of Science and Technology, Huainan 232000, Anhui, China.
  • 4 School of Medicine, Anhui University of Science and Technology, Huainan 232000, Anhui, China,; The First Affiliated Hospital of Anhui University of Science and Technology Huainan First People's Hospital, School of Medicine, Huainan 232000, Anhui, China.
  • 5 School of Medicine, Anhui University of Science and Technology, Huainan 232000, Anhui, China,; The First Affiliated Hospital of Anhui University of Science and Technology Huainan First People's Hospital, School of Medicine, Huainan 232000, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan 232000, Anhui, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, AUST, Huainan 232000, Anhui, China; Key Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and Technology, Huainan 232000, Anhui, China.
  • 6 The First Affiliated Hospital of Anhui University of Science and Technology Huainan First People's Hospital, School of Medicine, Huainan 232000, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan 232000, Anhui, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, AUST, Huainan 232000, Anhui, China; Key Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and Technology, Huainan 232000, Anhui, China; Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 232001, Anhui, China.. Electronic address: [email protected].
  • 7 The Affiliated Bozhou Hospital of Anhui University of Science and Technology (The People's Hospital of Bozhou). Bozhou, 236800, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan 232000, Anhui, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, AUST, Huainan 232000, Anhui, China; Key Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and Technology, Huainan 232000, Anhui, China; Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 232001, Anhui, China.. Electronic address: [email protected].
PMID: 41237696 DOI: 10.1016/j.intimp.2025.115812
Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disorder with limited effective therapeutic options. In this study, differential gene expression analysis of lung tissues from IPF patients and alveolar type 2 (AT2) cells identified BI-2536 as a potential therapeutic candidate for IPF. In an in vivo model, BI-2536 significantly ameliorated bleomycin (BLM)-induced pulmonary function decline in IPF mice while suppressing pulmonary inflammation and fibrosis markers, thereby mitigating pathological lung tissue damage. Further investigations revealed that polo-like kinase 2 (PLK2) serves as a key target of BI-2536, with Gly92 identified as a critical binding residue. Mechanistically, BI-2536 binds to PLK2, inhibiting downstream phosphorylation of JNK1/2 and SP1, consequently suppressing BLM-induced epithelial-mesenchymal transition (EMT) and fibrotic progression in AT2 cells. In summary, this study demonstrates that BI-2536 delays IPF progression by inhibiting the PLK2/JNK/SP1 signaling pathway in AT2 cells, providing a novel therapeutic agent and target for pulmonary fibrosis treatment.

Keywords

Gly92; Idiopathic pulmonary fibrosis(IPF);BI-2536; JNK/SP1; Polo-like kinase 2 (PLK2).

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