Novel mitophagy inducer TJ0113 alleviates pulmonary inflammation during acute lung injury
IntroductionAcute lung injury (ALI) is a severe respiratory disease with limited effective therapeutic options. Recent studies have highlighted mitochondrial damage as a crucial factor in the progression of ALI. Mitophagy, which facilitates the removal of damaged mitochondria, has been shown to redu...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1590458/full |
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| author | Zhengyuan Liu Danruo Fang Kaijun Chen Lingling Dong Huaqiong Huang Zhihua Chen |
| author_facet | Zhengyuan Liu Danruo Fang Kaijun Chen Lingling Dong Huaqiong Huang Zhihua Chen |
| author_sort | Zhengyuan Liu |
| collection | DOAJ |
| description | IntroductionAcute lung injury (ALI) is a severe respiratory disease with limited effective therapeutic options. Recent studies have highlighted mitochondrial damage as a crucial factor in the progression of ALI. Mitophagy, which facilitates the removal of damaged mitochondria, has been shown to reduce inflammation. Our collaborators constructed a small molecule mitophagy inducer, TJ0113. TJ0113 has been approved to initiate a Phase I clinical trial for Alport syndrome and a Phase II trial for Parkinson's disease in China. Therefore, we explored the potential of TJ0113 as a novel therapeutic for ALI.MethodsThe mitophagy-inducing potential of TJ0113 was assessed in HEK293T cells. The anti-inflammatory effects of TJ0113 were further evaluated in vivo using a mouse model of lipopolysaccharide (LPS)-induced ALI and in vitro using LPS-stimulated bone-marrow-derived macrophages (BMDMs).ResultsTJ0113 selectively induced mitophagy in damaged mitochondria. Furthermore, the PINK1–Parkin pathway was identified as a specific mitophagy pathway induced by TJ0113. In LPS-induced ALI mouse model, intraperitoneal injection of TJ0113 significantly reduced lung inflammation and mortality. In vitro, TJ0113 significantly inhibited the expression of LPS-induced inflammatory cytokines in BMDMs. Finally, we found that TJ0113 inhibited LPS-induced inflammation by inducing mitophagy and inhibiting nuclear factor κB (NF-κB) and inflammasome activation.ConclusionTJ0113 alleviates LPS-induced inflammation by inducing mitophagy and inhibiting NF-κB and inflammasome activation. Its selective action on damaged mitochondria suggests minimal side effects, positioning TJ0113 as a promising therapeutic candidate for ALI. |
| format | Article |
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| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-c96563ddfe7a489d8fadd001b6344a3d2025-08-20T04:00:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.15904581590458Novel mitophagy inducer TJ0113 alleviates pulmonary inflammation during acute lung injuryZhengyuan LiuDanruo FangKaijun ChenLingling DongHuaqiong HuangZhihua ChenIntroductionAcute lung injury (ALI) is a severe respiratory disease with limited effective therapeutic options. Recent studies have highlighted mitochondrial damage as a crucial factor in the progression of ALI. Mitophagy, which facilitates the removal of damaged mitochondria, has been shown to reduce inflammation. Our collaborators constructed a small molecule mitophagy inducer, TJ0113. TJ0113 has been approved to initiate a Phase I clinical trial for Alport syndrome and a Phase II trial for Parkinson's disease in China. Therefore, we explored the potential of TJ0113 as a novel therapeutic for ALI.MethodsThe mitophagy-inducing potential of TJ0113 was assessed in HEK293T cells. The anti-inflammatory effects of TJ0113 were further evaluated in vivo using a mouse model of lipopolysaccharide (LPS)-induced ALI and in vitro using LPS-stimulated bone-marrow-derived macrophages (BMDMs).ResultsTJ0113 selectively induced mitophagy in damaged mitochondria. Furthermore, the PINK1–Parkin pathway was identified as a specific mitophagy pathway induced by TJ0113. In LPS-induced ALI mouse model, intraperitoneal injection of TJ0113 significantly reduced lung inflammation and mortality. In vitro, TJ0113 significantly inhibited the expression of LPS-induced inflammatory cytokines in BMDMs. Finally, we found that TJ0113 inhibited LPS-induced inflammation by inducing mitophagy and inhibiting nuclear factor κB (NF-κB) and inflammasome activation.ConclusionTJ0113 alleviates LPS-induced inflammation by inducing mitophagy and inhibiting NF-κB and inflammasome activation. Its selective action on damaged mitochondria suggests minimal side effects, positioning TJ0113 as a promising therapeutic candidate for ALI.https://www.frontiersin.org/articles/10.3389/fphar.2025.1590458/fullacute lung injurymitophagy inducerTJ0113NF-κBNLRP3 inflammasome |
| spellingShingle | Zhengyuan Liu Danruo Fang Kaijun Chen Lingling Dong Huaqiong Huang Zhihua Chen Novel mitophagy inducer TJ0113 alleviates pulmonary inflammation during acute lung injury Frontiers in Pharmacology acute lung injury mitophagy inducer TJ0113 NF-κB NLRP3 inflammasome |
| title | Novel mitophagy inducer TJ0113 alleviates pulmonary inflammation during acute lung injury |
| title_full | Novel mitophagy inducer TJ0113 alleviates pulmonary inflammation during acute lung injury |
| title_fullStr | Novel mitophagy inducer TJ0113 alleviates pulmonary inflammation during acute lung injury |
| title_full_unstemmed | Novel mitophagy inducer TJ0113 alleviates pulmonary inflammation during acute lung injury |
| title_short | Novel mitophagy inducer TJ0113 alleviates pulmonary inflammation during acute lung injury |
| title_sort | novel mitophagy inducer tj0113 alleviates pulmonary inflammation during acute lung injury |
| topic | acute lung injury mitophagy inducer TJ0113 NF-κB NLRP3 inflammasome |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1590458/full |
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