ArticleThe Journal of clinical investigation2021
Hypoxia-inducible factor-1α-dependent induction of miR122 enhances hepatic ischemia tolerance.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Identification of HIF1A as a therapeutic target during SARS-CoV-2-associated lung injury.JCI insight · 2025Trial
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Serum miR-381-3p: Diagnostic Role and Mechanisms in Liver Transplant Ischemia-reperfusion Injury.Journal of clinical and translational hepatology · 2026Article
- PANoptosis nexus in ischemia-reperfusion injury: from integrated cell death mechanisms to novel therapeutic opportunities.Frontiers in immunology · 2026Review
- Hepatic ischemia-reperfusion injury: Underlying mechanisms and concepts in liver surgery and liver transplantation.Hepatology (Baltimore, Md.) · 2025Article
- Hypoxia signaling in the adipose tissue.Journal of molecular cell biology · 2025Review
- Progressive Deactivation of Hydroxylases Controls Hypoxia-Inducible Factor-1α-Coordinated Cellular Adaptation to Graded Hypoxia.Research (Washington, D.C.) · 2025Article
- Therapeutic targeting of hypoxia inducible factor in acute respiratory distress syndrome.The Journal of physiology · 2024Review
- HIF-2α-dependent induction of miR-29a restrains TNature communications · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Donor-specific graft injury in solid organ transplantation: potential mechanisms and therapeutic strategies.Frontiers in transplantation · 2024Article
- Hypoxia-adenosine axis as therapeutic targets for acute respiratory distress syndrome.Frontiers in immunology · 2024Review
- Interplay of hypoxia-inducible factors and oxygen therapy in cardiovascular medicine.Nature reviews. Cardiology · 2023Review
- Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury.World journal of gastroenterology · 2023Review
- TRIM37 exacerbates hepatic ischemia/reperfusion injury by facilitating IKKγ translocation.Molecular medicine (Cambridge, Mass.) · 2023Article
- Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner.International journal of biological sciences · 2023Article
- From cerebral ischemia towards myocardial, renal, and hepatic ischemia: Exosomal miRNAs as a general concept of intercellular communication in ischemia-reperfusion injury.Molecular therapy. Nucleic acids · 2022Review
- The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.Biomedicines · 2022Review
- Co-regulation of circadian clock genes and microRNAs in bone metabolism.Journal of Zhejiang University. Science. B · 2022Review
- Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments.Aging and disease · 2022Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Hepatic ischemia and reperfusion (IR) injury contributes to the morbidity and mortality associated with liver transplantation. microRNAs (miRNAs) constitute a family of noncoding RNAs that regulate gene expression at the posttranslational level through the repression of specific target genes. Here, we hypothesized that miRNAs could be targeted to enhance hepatic ischemia tolerance. A miRNA screen in a murine model of hepatic IR injury pointed us toward the liver-specific miRNA miR122. Subsequent studies in mice with hepatocyte-specific deletion of miR122 (miR122loxP/loxP Alb-Cre+ mice) during hepatic ischemia and reperfusion revealed exacerbated liver injury. Transcriptional studies implicated hypoxia-inducible factor-1α (HIF1α) in the induction of miR122 and identified the oxygen-sensing prolyl hydroxylase domain 1 (PHD1) as a miR122 target. Further studies indicated that HIF1α-dependent induction of miR122 participated in a feed-forward pathway for liver protection via the enhancement of hepatic HIF responses through PHD1 repression. Moreover, pharmacologic studies utilizing nanoparticle-mediated miR122 overexpression demonstrated attenuated liver injury. Finally, proof-of-principle studies in patients undergoing orthotopic liver transplantation showed elevated miR122 levels in conjunction with the repression of PHD1 in post-ischemic liver biopsies. Taken together, the present findings provide molecular insight into the functional role of miR122 in enhancing hepatic ischemia tolerance and suggest the potential utility of pharmacologic interventions targeting miR122 to dampen hepatic injury during liver transplantation.
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