ArticleJournal of biomedical science2023
The miR-15b-Smurf2-HSP27 axis promotes pulmonary fibrosis.
Article in Journal of biomedical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Ac-SDKP modulates apoptosis via HSP27 and the FAS/FASL and mitochondrial axes.Animal models and experimental medicine · 2026Article
- Research progresses on the regulatory roles of microRNAs in radiation-induced pulmonary fibrosis.Journal of molecular histology · 2026Review
- Smurf2 knockdown attenuates the progression of diabetic nephropathy by inhibiting mesangial cell proliferation and fibrosis through suppressing EYA2 ubiquitination.Renal failure · 2025Article
- SARS-CoV-2-encoded miR-nsp3-3p promotes pulmonary fibrosis by inhibiting expression of ALCAM.Virologica Sinica · 2025Article
- SAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse model.Cell death discovery · 2025Article
- GTSE1-driven ZEB1 stabilization promotes pulmonary fibrosis through the epithelial-to-mesenchymal transition.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Identification and Validation of Genes Exhibiting Dynamic Alterations in Response to Bleomycin-Induced Pulmonary Fibrosis.Molecular biotechnology · 2024Article
- Assessing the impact of triiodothyronine treatment on the lung microbiome of mice with pulmonary fibrosis.BMC pulmonary medicine · 2024Article
- Standigm ASK™: knowledge graph and artificial intelligence platform applied to target discovery in idiopathic pulmonary fibrosis.Briefings in bioinformatics · 2024Article
- Crosstalk of ubiquitin system and non-coding RNA in fibrosis.International journal of biological sciences · 2024Review
- Drug like HSP27 cross linkers with chromenone structure ameliorates pulmonary fibrosis.Frontiers in pharmacology · 2023Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHeat shock protein 27 (HSP27) is overexpressed during pulmonary fibrosis (PF) and exacerbates PF; however, the upregulation of HSP27 during PF and the therapeutic strategy of HSP27 inhibition is not well elucidated.
methodsWe have developed a mouse model simulating clinical stereotactic body radiotherapy (SBRT) with focal irradiation and validated the induction of RIPF. HSP25 (murine form of HSP27) transgenic (TG) and LLC1-derived orthotropic lung tumor models were also used. Lung tissues of patients with RIPF and idiopathic pulmonary fibrosis, and lung tissues from various fibrotic mouse models, as well as appropriated cell line systems were used. Public available gene expression datasets were used for therapeutic response rate analysis. A synthetic small molecule HSP27 inhibitor, J2 was also used.
resultsHSP27 expression with its phosphorylated form (pHSP27) increased during PF. Decreased mRNA expression of SMAD-specific E3 ubiquitin-protein ligase 2 (Smurf2), which is involved in ubiquitin degradation of HSP27, was responsible for the increased expression of pHSP27. In addition, increased expression of miRNA15b was identified with decreased expression of Smurf2 mRNA in PF models. Inverse correlation between pHSP27 and Smurf2 was observed in the lung tissues of PF animals, an irradiated orthotropic lung cancer models, and PF tissues from patients. Moreover, a HSP27 inhibitor cross-linked with HSP27 protein to ameliorate PF, which was more effective when targeting the epithelial to mesenchymal transition (EMT) stage of PF.
conclusionsOur findings identify upregulation mechanisms of HSP27 during PF and provide a therapeutic strategy for HSP27 inhibition for overcoming PF.
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