Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axis
Renal fibrosis is a major pathological feature of chronic kidney disease (CKD). While emodin is reported to elicit anti-fibrotic effects on renal injury, little is known about its effects on microRNA (miRNA)-modulated mechanisms in renal fibrosis. In this study, we established a unilateral ureteral...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1042093/full |
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| author | Liulin Wang Liulin Wang Liulin Wang Xuerui Wang Xuerui Wang Xuerui Wang Gang Li Gang Li Gang Li Shanshan Zhou Shanshan Zhou Shanshan Zhou Rui Wang Rui Wang Rui Wang Qi Long Qi Long Qi Long Min Wang Min Wang Min Wang Liang Li Liang Li Liang Li Hai Huang Hai Huang Hai Huang Yuanming Ba Yuanming Ba Yuanming Ba |
| author_facet | Liulin Wang Liulin Wang Liulin Wang Xuerui Wang Xuerui Wang Xuerui Wang Gang Li Gang Li Gang Li Shanshan Zhou Shanshan Zhou Shanshan Zhou Rui Wang Rui Wang Rui Wang Qi Long Qi Long Qi Long Min Wang Min Wang Min Wang Liang Li Liang Li Liang Li Hai Huang Hai Huang Hai Huang Yuanming Ba Yuanming Ba Yuanming Ba |
| author_sort | Liulin Wang |
| collection | DOAJ |
| description | Renal fibrosis is a major pathological feature of chronic kidney disease (CKD). While emodin is reported to elicit anti-fibrotic effects on renal injury, little is known about its effects on microRNA (miRNA)-modulated mechanisms in renal fibrosis. In this study, we established a unilateral ureteral obstruction (UUO) model and a transforming growth factor (TGF)-β1-induced normal rat renal tubular epithelial cell line (NRK-52E) model to investigate the protective effects of emodin on renal fibrosis and its miRNA/target gene mechanisms. Dual-luciferase assay was performed to confirm the direct binding of miRNA and target genes in HEK293 cells. Results showed that oral administration of emodin significantly ameliorated the loss of body weight and the increase in physicochemical parameters, including serum uric acid, creatinine, and urea nitrogen in UUO mice. Inflammatory cytokines, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin (IL)-1β, but not IL-6, were down-regulated by emodin administration. Emodin decreased the expression levels of TGF-β1 and fibrotic-related proteins, including alpha-smooth muscle actin, Collagen IV, and Fibronectin, and increased the expression of E-cadherin. Furthermore, miR-490-3p was decreased in UUO mice and negatively correlated with increased expression of high migration protein A2 (HMGA2). We further confirmed HMGA2 was the target of miR-490-3p. Transfection of miR-490-3p mimics decreased, while transfection of miR-490-3p inhibitors increased fibrotic-related proteins and HMGA2 expression levels in TGF-β1-induced NRK-52E cells. Furthermore, transfection of miR-490-3p mimics enhanced the anti-fibrotic effects of emodin, while transfection of miR-490-3p inhibitors abolished the protective effects of emodin. Thus, as a novel target of emodin that prevents renal fibrosis in the HMGA2-dependent signaling pathway, miR-490-3p has potential implications in CKD pathology. |
| first_indexed | 2024-04-10T06:02:51Z |
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| language | English |
| last_indexed | 2024-04-10T06:02:51Z |
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| spelling | doaj.art-8503b0830e904f5197d3e4d8b4d744552023-03-03T06:42:40ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.10420931042093Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axisLiulin Wang0Liulin Wang1Liulin Wang2Xuerui Wang3Xuerui Wang4Xuerui Wang5Gang Li6Gang Li7Gang Li8Shanshan Zhou9Shanshan Zhou10Shanshan Zhou11Rui Wang12Rui Wang13Rui Wang14Qi Long15Qi Long16Qi Long17Min Wang18Min Wang19Min Wang20Liang Li21Liang Li22Liang Li23Hai Huang24Hai Huang25Hai Huang26Yuanming Ba27Yuanming Ba28Yuanming Ba29Hubei Provincial Hospital of Tranditional Chinese Medicine, Wuhan, ChinaAffiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Academy of Traditional Chinese Medicine, Wuhan, ChinaBeijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Basic Research With Traditional Chinese Medicine on Infectious Diseases, Beijing, ChinaBeijing Institute of Chinese Medicine, Beijing, ChinaHubei Provincial Hospital of Tranditional Chinese Medicine, Wuhan, ChinaAffiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Academy of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Hospital of Tranditional Chinese Medicine, Wuhan, ChinaAffiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Academy of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Hospital of Tranditional Chinese Medicine, Wuhan, ChinaAffiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Academy of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Hospital of Tranditional Chinese Medicine, Wuhan, ChinaAffiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Academy of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Hospital of Tranditional Chinese Medicine, Wuhan, ChinaAffiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Academy of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Hospital of Tranditional Chinese Medicine, Wuhan, ChinaAffiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Academy of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Hospital of Tranditional Chinese Medicine, Wuhan, ChinaAffiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Academy of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Hospital of Tranditional Chinese Medicine, Wuhan, ChinaAffiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, ChinaHubei Provincial Academy of Traditional Chinese Medicine, Wuhan, ChinaRenal fibrosis is a major pathological feature of chronic kidney disease (CKD). While emodin is reported to elicit anti-fibrotic effects on renal injury, little is known about its effects on microRNA (miRNA)-modulated mechanisms in renal fibrosis. In this study, we established a unilateral ureteral obstruction (UUO) model and a transforming growth factor (TGF)-β1-induced normal rat renal tubular epithelial cell line (NRK-52E) model to investigate the protective effects of emodin on renal fibrosis and its miRNA/target gene mechanisms. Dual-luciferase assay was performed to confirm the direct binding of miRNA and target genes in HEK293 cells. Results showed that oral administration of emodin significantly ameliorated the loss of body weight and the increase in physicochemical parameters, including serum uric acid, creatinine, and urea nitrogen in UUO mice. Inflammatory cytokines, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin (IL)-1β, but not IL-6, were down-regulated by emodin administration. Emodin decreased the expression levels of TGF-β1 and fibrotic-related proteins, including alpha-smooth muscle actin, Collagen IV, and Fibronectin, and increased the expression of E-cadherin. Furthermore, miR-490-3p was decreased in UUO mice and negatively correlated with increased expression of high migration protein A2 (HMGA2). We further confirmed HMGA2 was the target of miR-490-3p. Transfection of miR-490-3p mimics decreased, while transfection of miR-490-3p inhibitors increased fibrotic-related proteins and HMGA2 expression levels in TGF-β1-induced NRK-52E cells. Furthermore, transfection of miR-490-3p mimics enhanced the anti-fibrotic effects of emodin, while transfection of miR-490-3p inhibitors abolished the protective effects of emodin. Thus, as a novel target of emodin that prevents renal fibrosis in the HMGA2-dependent signaling pathway, miR-490-3p has potential implications in CKD pathology.https://www.frontiersin.org/articles/10.3389/fphar.2023.1042093/fullemodinrenal fibrosismicroRNAinflammatory factorHMGA2 |
| spellingShingle | Liulin Wang Liulin Wang Liulin Wang Xuerui Wang Xuerui Wang Xuerui Wang Gang Li Gang Li Gang Li Shanshan Zhou Shanshan Zhou Shanshan Zhou Rui Wang Rui Wang Rui Wang Qi Long Qi Long Qi Long Min Wang Min Wang Min Wang Liang Li Liang Li Liang Li Hai Huang Hai Huang Hai Huang Yuanming Ba Yuanming Ba Yuanming Ba Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axis Frontiers in Pharmacology emodin renal fibrosis microRNA inflammatory factor HMGA2 |
| title | Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axis |
| title_full | Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axis |
| title_fullStr | Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axis |
| title_full_unstemmed | Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axis |
| title_short | Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axis |
| title_sort | emodin ameliorates renal injury and fibrosis via regulating the mir 490 3p hmga2 axis |
| topic | emodin renal fibrosis microRNA inflammatory factor HMGA2 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1042093/full |
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