Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathway
BackgroundRenal interstitial fibrosis (RIF) represents the final common pathway in nearly all progressive chronic kidney diseases. This study aimed to investigate the effects of Yishen-Huoxue formula (YHF) on RIF and its underlying mechanisms.MethodsUnilateral ureteral obstruction (UUO) model was ap...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1530092/full |
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| author | Mouying Du Chun Yao Qinke Lv Aimei Gong Yonghua Zhu Jiayuan Li Jian Zhong |
| author_facet | Mouying Du Chun Yao Qinke Lv Aimei Gong Yonghua Zhu Jiayuan Li Jian Zhong |
| author_sort | Mouying Du |
| collection | DOAJ |
| description | BackgroundRenal interstitial fibrosis (RIF) represents the final common pathway in nearly all progressive chronic kidney diseases. This study aimed to investigate the effects of Yishen-Huoxue formula (YHF) on RIF and its underlying mechanisms.MethodsUnilateral ureteral obstruction (UUO) model was applied to induce RIF in vivo. Thirty-six male SD rats were randomized into six groups: sham group, UUO group, UUO + Losartan group, and UUO + YHF-L/M/H groups. The histopathological changes of rat kidney and its function were evaluated 14 days post-UUO. miRNA sequencing and differential gene analysis identified miR-210 as a potential target of YHF treatment. Western blot and qRT-PCR were employed to assess the impact of miR-210 overexpression and knockdown on the expression of hypoxia-related factors in HK-2, NRK-52E, HUVEC, and 293T cells under hypoxic conditions. Cell proliferation, migration, and angiogenesis were determined using CCK-8 assays, transwell assays, and tubule formation assays, respectively.ResultsIn vivo, YHF treatment significantly attenuated RIF, protected renal function, increased miR-210 expression, and decreased the expression of HIF-1α, BNIP3, and NIX in the serum exosomes of UUO rats. In vitro experiments revealed that miR-210 downregulates the expression of HIF-1α and its downstream factors, mitigating hypoxia-induced cellular injuries, including decreased cell viability, migration ability, and angiogenesis capability. Further experiments demonstrated that YHF treatment upregulated miR-210 expression while downregulating HIF-1α expression in HK-2 cells under hypoxic conditions. Meanwhile, YHF alleviated hypoxia-induced renal cell damage and impaired angiogenesis in HUVECs, with miR-210 mimic enhancing and miR-210 inhibitor attenuating these protective effects.ConclusionYishen-Huoxue formula alleviates RIF by mediating the miR-210/HIF-1α pathway to attenuate hypoxia-induced renal cell injury and promote angiogenesis. |
| format | Article |
| id | doaj-art-fd24094b722e411baa4f56988a4fa85b |
| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-fd24094b722e411baa4f56988a4fa85b2025-08-20T03:47:27ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-05-011010.3389/fmed.2025.15300921530092Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathwayMouying Du0Chun Yao1Qinke Lv2Aimei Gong3Yonghua Zhu4Jiayuan Li5Jian Zhong6Graduate School, Guangxi University of Traditional Chinese Medicine, Nanning, ChinaGuangxi University of Traditional Chinese Medicine, Nanning, ChinaGraduate School, Guangxi University of Traditional Chinese Medicine, Nanning, ChinaDepartment of Nephrology, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, ChinaGraduate School, Guangxi University of Traditional Chinese Medicine, Nanning, ChinaGraduate School, Guangxi University of Traditional Chinese Medicine, Nanning, ChinaDepartment of Nephrology, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, ChinaBackgroundRenal interstitial fibrosis (RIF) represents the final common pathway in nearly all progressive chronic kidney diseases. This study aimed to investigate the effects of Yishen-Huoxue formula (YHF) on RIF and its underlying mechanisms.MethodsUnilateral ureteral obstruction (UUO) model was applied to induce RIF in vivo. Thirty-six male SD rats were randomized into six groups: sham group, UUO group, UUO + Losartan group, and UUO + YHF-L/M/H groups. The histopathological changes of rat kidney and its function were evaluated 14 days post-UUO. miRNA sequencing and differential gene analysis identified miR-210 as a potential target of YHF treatment. Western blot and qRT-PCR were employed to assess the impact of miR-210 overexpression and knockdown on the expression of hypoxia-related factors in HK-2, NRK-52E, HUVEC, and 293T cells under hypoxic conditions. Cell proliferation, migration, and angiogenesis were determined using CCK-8 assays, transwell assays, and tubule formation assays, respectively.ResultsIn vivo, YHF treatment significantly attenuated RIF, protected renal function, increased miR-210 expression, and decreased the expression of HIF-1α, BNIP3, and NIX in the serum exosomes of UUO rats. In vitro experiments revealed that miR-210 downregulates the expression of HIF-1α and its downstream factors, mitigating hypoxia-induced cellular injuries, including decreased cell viability, migration ability, and angiogenesis capability. Further experiments demonstrated that YHF treatment upregulated miR-210 expression while downregulating HIF-1α expression in HK-2 cells under hypoxic conditions. Meanwhile, YHF alleviated hypoxia-induced renal cell damage and impaired angiogenesis in HUVECs, with miR-210 mimic enhancing and miR-210 inhibitor attenuating these protective effects.ConclusionYishen-Huoxue formula alleviates RIF by mediating the miR-210/HIF-1α pathway to attenuate hypoxia-induced renal cell injury and promote angiogenesis.https://www.frontiersin.org/articles/10.3389/fmed.2025.1530092/fullrenal interstitial fibrosisYishen-Huoxue formulamiR-210HIF-1αhypoxia |
| spellingShingle | Mouying Du Chun Yao Qinke Lv Aimei Gong Yonghua Zhu Jiayuan Li Jian Zhong Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathway Frontiers in Medicine renal interstitial fibrosis Yishen-Huoxue formula miR-210 HIF-1α hypoxia |
| title | Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathway |
| title_full | Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathway |
| title_fullStr | Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathway |
| title_full_unstemmed | Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathway |
| title_short | Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathway |
| title_sort | yishen huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia induced renal cell injury and promoting angiogenesis via mir 210 hif 1α pathway |
| topic | renal interstitial fibrosis Yishen-Huoxue formula miR-210 HIF-1α hypoxia |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1530092/full |
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