Evidence mapPaperPMID 41433111Full record

ArticleKidney3602026

The Positive Feedback Loop of Hypoxia-Inducible Factor-1 α /miR-295/Factor Inhibiting Hypoxia-Inducible Factor-1 in Hyperuricemic Nephropathy.

Jiachang Li, Yuhan Ma, Yanni Wang, Yizhi Chen, JiaLi Wei

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Article in Kidney360, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Jiachang LiDepartment of Nephrology, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, Hainan, China.ORCID 0009-0008-4992-1210
Yuhan MaPSB Academy, Singapore.
Yanni WangDepartment of Nephrology, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, Hainan, China.
Yizhi ChenDepartment of Nephrology, Hainan Hospital of Chinese PLA General Hospital, Academician Chen Xiangmei of Hainan Province Kidney Diseases Research Team Innovation Center, Sanya, China.ORCID 0000-0003-1197-1999
JiaLi WeiDepartment of Nephrology, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, Hainan, China.

Funding

Hainan Provincial Health Science and Technology Innovation joint project of China SQ2023WSJK0153Key Research and Development Project of Hainan Province ZDYF2022SHFZ016National Natural Science Foundation of China Cultivation 530 Project Youth project: 2021QNXM12,13,17; General Program: 2021MSXM17Natural Science Foundation of China 82160135Natural Science Foundation of China 82360146Natural Science Foundation of Hainan Province 821MS0825Natural Science Foundation of Hainan Province 822QN455Natural Science Foundation of Hainan Province High Level Talent Project (821RC705)
6 · The paper itself

Abstract

key pointsHypoxia-inducible factor-1 α -mediated induction of miR-295 in renal tubular cells in hyperuricemic nephropathy. This study reveals a hypoxia-inducible factor-1 α /miR-295/factor inhibiting hypoxia-inducible factor-1 positive feedback loop that regulates tubular damage and fibrosis in hyperuricemic nephropathy.

backgroundHyperuricemia is a common metabolic disorder and a risk factor for multiple diseases, including CKD. Hyperuricemic nephropathy (HN) affects many individuals with hyperuricemia, yet its molecular mechanisms are not fully understood, and effective treatments are lacking.

methodsIn vitro , human tubular epithelial cells (HK-2) were exposed to uric acid for 36 hours, followed by transfection with microRNA mimic or factor inhibiting hypoxia-inducible factor-1 (FIH-1) siRNA. In vivo , HN was induced in mice using potassium oxonate and adenine for 2 weeks. miR-295 mimic or anti-miR-295 was administered through tail vein injection, and mice were euthanized for analysis.

resultsWe demonstrated a significant increase of miR-295 in renal tubular cells in HN mice. Hyperuricemia led to the activation of hypoxia inducible factor-1 α (HIF-1 α ), and inhibition of HIF-1 α by YC-1 (a HIF-1 α inhibitor) prevented the increase of miR-295. Chromatin immunoprecipitation assay further verified HIF-1 α binding to the miR-295 gene promoter directly. Functionally, inhibition of miR-295 led to increased cell death and tubulointerstitial fibrosis in HN mice, whereas supplementation of miR-295 mimic had kidney-protective effects in this model. miR-295 suppressed the expression of FIH-1) in both in vitro and in vivo models of HN. Luciferase microRNA target reporter assay further verified FIH-1 as a direct target of miR-295. In addition, knockdown of FIH-1 inhibits tubular cell apoptosis and profibrotic cytokines production in HK2 cells during uric acid treatment.

conclusionsThis study reveals a HIF-1 α /miR-295/FIH-1 positive feedback loop that regulates tubular damage and fibrosis in HN.

Indexed as

HyperuricemiaHypoxia-Inducible Factor 1, alpha SubunitKidney DiseasesMicroRNAsRepressor ProteinsAnimalsCell LineDisease Models, AnimalEpithelial CellsFeedback, PhysiologicalFibrosisHumansKidney TubulesMaleMiceMice, Inbred C57BLfactor inhibiting hypoxia-inducible factor 1, mouseHIF1A protein, humanHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitMicroRNAsMixed Function OxygenasesRepressor ProteinsUric Acidinterstitial fibrosisnephropathyrenal fibrosis

Identifiers

PMID41433111
PMCPMC13134801

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.