Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation
Pulmonary fibrosis is a chronic and progressive interstitial lung disease associated with the decay of pulmonary function, which leads to a fatal outcome. As an essential epigenetic regulator of DNA methylation, the involvement of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) in fi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-11-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.162831 |
| _version_ | 1797634346093379584 |
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| author | Demin Cheng Yue Wang Ziwei Li Haojie Xiong Wenqing Sun Sichuan Xi Siyun Zhou Yi Liu Chunhui Ni |
| author_facet | Demin Cheng Yue Wang Ziwei Li Haojie Xiong Wenqing Sun Sichuan Xi Siyun Zhou Yi Liu Chunhui Ni |
| author_sort | Demin Cheng |
| collection | DOAJ |
| description | Pulmonary fibrosis is a chronic and progressive interstitial lung disease associated with the decay of pulmonary function, which leads to a fatal outcome. As an essential epigenetic regulator of DNA methylation, the involvement of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) in fibroblast activation remains largely undefined in pulmonary fibrosis. In the present study, we found that TGF-β1–mediated upregulation of UHRF1 repressed beclin 1 via methylated induction of its promoter, which finally resulted in fibroblast activation and lung fibrosis both in vitro and in vivo. Moreover, knockdown of UHRF1 significantly arrested fibroblast proliferation and reactivated beclin 1 in lung fibroblasts. Thus, intravenous administration of UHRF1 siRNA–loaded liposomes significantly protected mice against experimental pulmonary fibrosis. Accordingly, our data suggest that UHRF1 might be a novel potential therapeutic target in the pathogenesis of pulmonary fibrosis. |
| first_indexed | 2024-03-11T12:06:23Z |
| format | Article |
| id | doaj.art-24b2b7c844e64b689a5c7dda836f4730 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:06:23Z |
| publishDate | 2022-11-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-24b2b7c844e64b689a5c7dda836f47302023-11-07T16:24:51ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-11-01722Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activationDemin ChengYue WangZiwei LiHaojie XiongWenqing SunSichuan XiSiyun ZhouYi LiuChunhui NiPulmonary fibrosis is a chronic and progressive interstitial lung disease associated with the decay of pulmonary function, which leads to a fatal outcome. As an essential epigenetic regulator of DNA methylation, the involvement of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) in fibroblast activation remains largely undefined in pulmonary fibrosis. In the present study, we found that TGF-β1–mediated upregulation of UHRF1 repressed beclin 1 via methylated induction of its promoter, which finally resulted in fibroblast activation and lung fibrosis both in vitro and in vivo. Moreover, knockdown of UHRF1 significantly arrested fibroblast proliferation and reactivated beclin 1 in lung fibroblasts. Thus, intravenous administration of UHRF1 siRNA–loaded liposomes significantly protected mice against experimental pulmonary fibrosis. Accordingly, our data suggest that UHRF1 might be a novel potential therapeutic target in the pathogenesis of pulmonary fibrosis.https://doi.org/10.1172/jci.insight.162831Pulmonology |
| spellingShingle | Demin Cheng Yue Wang Ziwei Li Haojie Xiong Wenqing Sun Sichuan Xi Siyun Zhou Yi Liu Chunhui Ni Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation JCI Insight Pulmonology |
| title | Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation |
| title_full | Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation |
| title_fullStr | Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation |
| title_full_unstemmed | Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation |
| title_short | Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation |
| title_sort | liposomal uhrf1 sirna shows lung fibrosis treatment potential through regulation of fibroblast activation |
| topic | Pulmonology |
| url | https://doi.org/10.1172/jci.insight.162831 |
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