LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization
Renal interstitial fibrosis (RIF) is a common pathological feature contributing to chronic injury and maladaptive repair following acute kidney injury. Currently, there is no effective therapy for RIF. We have reported that locked nuclear acid (LNA)-anti-miR-150 antagonizes pro-fibrotic pathways in...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.913007/full |
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| author | Xiangnan Hao Junjun Luan Congcong Jiao Cong Ma Zixuan Feng Lingzi Zhu Yixiao Zhang Jingqi Fu Enyin Lai Beiru Zhang Yanqiu Wang Jeffrey B. Kopp Jingbo Pi Hua Zhou |
| author_facet | Xiangnan Hao Junjun Luan Congcong Jiao Cong Ma Zixuan Feng Lingzi Zhu Yixiao Zhang Jingqi Fu Enyin Lai Beiru Zhang Yanqiu Wang Jeffrey B. Kopp Jingbo Pi Hua Zhou |
| author_sort | Xiangnan Hao |
| collection | DOAJ |
| description | Renal interstitial fibrosis (RIF) is a common pathological feature contributing to chronic injury and maladaptive repair following acute kidney injury. Currently, there is no effective therapy for RIF. We have reported that locked nuclear acid (LNA)-anti-miR-150 antagonizes pro-fibrotic pathways in human renal tubular cells by regulating the suppressor of cytokine signal 1 (SOCS1)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. In the present study, we aimed to clarify whether LNA-anti-miR-150 attenuates folic acid-induced RIF mice by regulating this pathway and by reducing pro-inflammatory M1/M2 macrophage polarization. We found that renal miR-150 was upregulated in folic acid-induced RIF mice at day 30 after injection. LNA-anti-miR-150 alleviated the degree of RIF, as shown by periodic acid–Schiff and Masson staining and by the expression of pro-fibrotic proteins, including alpha-smooth muscle actin and fibronectin. In RIF mice, SOCS1 was downregulated, and p-JAK1 and p-STAT1 were upregulated. LNA-anti-miR-150 reversed the changes in renal SOCS1, p-JAK1, and p-STAT1 expression. In addition, renal infiltration of total macrophages, pro-inflammatory M1 and M2 macrophages as well as their secreted cytokines were increased in RIF mice compared to control mice. Importantly, in folic acid-induced RIF mice, LNA-anti-miR-150 attenuated the renal infiltration of total macrophages and pro-inflammatory subsets, including M1 macrophages expressing CD11c and M2 macrophages expressing CD206. We conclude that the anti-renal fibrotic role of LNA-anti-miR-150 in folic acid-induced RIF mice may be mediated by reducing pro-inflammatory M1 and M2 macrophage polarization via the SOCS1/JAK1/STAT1 pathway. |
| first_indexed | 2024-12-10T17:18:44Z |
| format | Article |
| id | doaj.art-71300850a18d449888475e16a35f8e47 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T17:18:44Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-71300850a18d449888475e16a35f8e472022-12-22T01:40:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.913007913007LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarizationXiangnan Hao0Junjun Luan1Congcong Jiao2Cong Ma3Zixuan Feng4Lingzi Zhu5Yixiao Zhang6Jingqi Fu7Enyin Lai8Beiru Zhang9Yanqiu Wang10Jeffrey B. Kopp11Jingbo Pi12Hua Zhou13Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Urology, Shengjing Hospital of China Medical University, Shenyang, ChinaProgram of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, ChinaDepartment of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaKidney Disease Section, NIDDK/NIH, Bethesda, MD, United StatesProgram of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, ChinaDepartment of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaRenal interstitial fibrosis (RIF) is a common pathological feature contributing to chronic injury and maladaptive repair following acute kidney injury. Currently, there is no effective therapy for RIF. We have reported that locked nuclear acid (LNA)-anti-miR-150 antagonizes pro-fibrotic pathways in human renal tubular cells by regulating the suppressor of cytokine signal 1 (SOCS1)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. In the present study, we aimed to clarify whether LNA-anti-miR-150 attenuates folic acid-induced RIF mice by regulating this pathway and by reducing pro-inflammatory M1/M2 macrophage polarization. We found that renal miR-150 was upregulated in folic acid-induced RIF mice at day 30 after injection. LNA-anti-miR-150 alleviated the degree of RIF, as shown by periodic acid–Schiff and Masson staining and by the expression of pro-fibrotic proteins, including alpha-smooth muscle actin and fibronectin. In RIF mice, SOCS1 was downregulated, and p-JAK1 and p-STAT1 were upregulated. LNA-anti-miR-150 reversed the changes in renal SOCS1, p-JAK1, and p-STAT1 expression. In addition, renal infiltration of total macrophages, pro-inflammatory M1 and M2 macrophages as well as their secreted cytokines were increased in RIF mice compared to control mice. Importantly, in folic acid-induced RIF mice, LNA-anti-miR-150 attenuated the renal infiltration of total macrophages and pro-inflammatory subsets, including M1 macrophages expressing CD11c and M2 macrophages expressing CD206. We conclude that the anti-renal fibrotic role of LNA-anti-miR-150 in folic acid-induced RIF mice may be mediated by reducing pro-inflammatory M1 and M2 macrophage polarization via the SOCS1/JAK1/STAT1 pathway.https://www.frontiersin.org/articles/10.3389/fimmu.2022.913007/fullLNA-anti-miR-150folic acidSOCS1/JAK1/STAT1M1/M2 macrophage polarizationrenal fibrosis |
| spellingShingle | Xiangnan Hao Junjun Luan Congcong Jiao Cong Ma Zixuan Feng Lingzi Zhu Yixiao Zhang Jingqi Fu Enyin Lai Beiru Zhang Yanqiu Wang Jeffrey B. Kopp Jingbo Pi Hua Zhou LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization Frontiers in Immunology LNA-anti-miR-150 folic acid SOCS1/JAK1/STAT1 M1/M2 macrophage polarization renal fibrosis |
| title | LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization |
| title_full | LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization |
| title_fullStr | LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization |
| title_full_unstemmed | LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization |
| title_short | LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization |
| title_sort | lna anti mir 150 alleviates renal interstitial fibrosis by reducing pro inflammatory m1 m2 macrophage polarization |
| topic | LNA-anti-miR-150 folic acid SOCS1/JAK1/STAT1 M1/M2 macrophage polarization renal fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.913007/full |
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