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miR-150-Based RNA Interference Attenuates Tubulointerstitial Fibrosis through the SOCS1/JAK/STAT Pathway In Vivo and In Vitro.
Luan, Junjun; Fu, Jingqi; Wang, Dongdong; Jiao, Congcong; Cui, Xiangfei; Chen, Chengjie; Liu, Dan; Zhang, Yixiao; Wang, Yanqiu; Yuen, Peter S T; Kopp, Jeffrey B; Pi, Jingbo; Zhou, Hua.
Afiliación
  • Luan J; Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
  • Fu J; Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, China.
  • Wang D; Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
  • Jiao C; Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
  • Cui X; Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
  • Chen C; Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, China.
  • Liu D; Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, China.
  • Zhang Y; Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China.
  • Wang Y; Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
  • Yuen PST; Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, MD, USA.
  • Kopp JB; Kidney Disease Section, NIDDK, NIH, Bethesda, MD, USA.
  • Pi J; Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, China.
  • Zhou H; Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
Mol Ther Nucleic Acids ; 22: 871-884, 2020 Dec 04.
Article en En | MEDLINE | ID: mdl-33230482
We investigated whether microRNA-150 (miR-150)-based RNA interference (RNAi) ameliorates tubular injury and tubulointerstitial fibrosis. Mice injected with folic acid developed tubulointerstitial fibrosis at day 30. miR-150 levels were increased at day 7 and peaked at day 30. At day 30, protein levels of α-smooth muscle actin, fibronectin (FN), and collagen 1 (COL-1) were increased, while suppressor of cytokine signal 1 (SOCS1) was decreased. Kidneys manifested increased macrophage numbers and increased expression of potential mediators: interferon-γ, interleukin-6, and tumor necrosis factor-α. Locked nucleic acid-anti-miR-150, started prior to or after tubular injury and administered twice weekly for 4 weeks, reversed renal inflammation and fibrosis. In HK-2 cells, co-culture with macrophages increased miR-150 expression and decreased SOCS1. Janus kinase (JAK) and signal transducer and activators of transcription (STAT) pathway-related proteins p-JAK1, p-JAK2, p-STAT1, p-STAT3, and pro-fibrotic genes encoding α-smooth muscle actin, FN, and COL-1 were all upregulated. The miR-150 antagonist reversed these transcriptional changes. Lastly, in renal biopsies from patients with chronic interstitial fibrosis, renal miR-150, and pro-fibrotic gene expression and macrophage numbers were increased, while SOCS1 expression was decreased. In conclusion, miR-150-based RNAi is as a potential novel therapeutic agent for tubulointerstitial fibrosis, suppressing the SOCS1/JAK/STAT pathway and reducing macrophage influx.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos