ORIGINAL RESEARCH article
Front. Med.
Sec. Nephrology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1530092
Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathway
Provisionally accepted
- 1Guangxi University of Chinese Medicine, Nanning, Guangx, China
- 2First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, China
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Background: Renal 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. Methods: Unilateral 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. Results: In 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. Conclusion: YHF alleviates RIF by mediating the miR-210/HIF-1α pathway to attenuate hypoxia-induced renal cell injury and promote angiogenesis.
Keywords: Renal interstitial fibrosis, Yishen-Huoxue formula, miR-210, HIF-1α, hypoxia
Received: 18 Nov 2024; Accepted: 21 Apr 2025.
Copyright: © 2025 Du, Lv, Gong, Zhu, Li, Yao and Zhong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jian Zhong, First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, China
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