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Cited by 163Acute Kidney Injury ResearchRenal Transplantation Outcomes and TreatmentsOrgan Transplantation Techniques and Outcomes

Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival

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Conde, Elisa, Alegre, Laura, Blanco-Sánchez, Ignacio, Sáenz-Morales, David, Aguado-Fraile, Elia, Ponte, Belén, Ramos, Edurne, Sáiz, Ana +9 more·2012·PLoS ONE
DOI 10.1371/journal.pone.0033258PMC PMC3303832
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Abstract

Acute tubular necrosis (ATN) caused by ischemia/reperfusion (I/R) during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α), using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.

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  • Other studies have demonstrated that HIF-1α levels decrease over time after I/R.

    “other studies have also demonstrated that HIF-1α levels decrease over time after I/R (Conde et al., 2012).”

    From Material-dependent oxygen transport governs ischemia-reperfusion injury and drug response in a kidney microphysiological system (2026) · cites this paper as Conde et al., 2012

    The Results section, “HIF-1α is induced after ischemia and during reperfusion in vivo” (page unavailable), reports HIF-1α expression during reperfusion at days 3, 5, and 7, rather than a decrease over time after I/R. The Discussion also describes significant HIF-1α protein accumulation during reperfusion. (LLM, conf=0.86)

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  • HIF-1α induction during reperfusion plays a role in preventing inappropriate repair following renal I/R, making it a critical cellular response to ischemia.

    “it has been reported that HIF-1α induction during reperfusion plays a role in preventing inappropriate repair following renal I/R (Conde et al., 2012), making it a critical cellular response to ischemia.”

    From Material-dependent oxygen transport governs ischemia-reperfusion injury and drug response in a kidney microphysiological system (2026) · cites this paper as Conde et al., 2012

    The Discussion (page not available in our copy) says reperfusion-induced HIF-1α is crucial for proximal tubule cell survival and recovery after renal I/R. The Results also report greater tubular damage when HIF-1α is inhibited. These passages support its role in repair, but do not specifically establish that it prevents inappropriate repair. (LLM, conf=0.84)

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Research works printed but not linked: 34

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Authors
Conde, E., Alegre, L., Blanco-Sánchez, I., Sáenz-Morales, D., Aguado-Fraile, E., Ponte, B., Ramos, E., Sáiz, A., Jiménez, C., Ordoñez, A., López-Cabrera, M., Peso, L. D., de Landázuri, M. O., Liaño, F., Selgas, R., Sanchez-Tomero, J. A., & García-Bermejo, M. L.
Affiliations
  • Instituto Ramón y Cajal de Investigación Sanitaria (ES)
  • Hospital Universitario La Paz (ES)
  • Consejo Superior de Investigaciones Científicas (ES)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-03-14
Volume
7
Issue
3
Pages
e33258
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0033258
PMC
PMC3303832
OpenAlex
W2107468794
Cited by
163
References
0
Citations by year
2026: 9 · 2025: 1 · 2024: 4 · 2023: 12 · 2022: 16 · 2021: 18 · 2020: 23 · 2019: 15 · 2018: 13 · 2017: 10 · 2016: 16 · 2015: 8 · 2014: 9 · 2013: 5 · 2012: 4
FWCI
6.18
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
  • Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion, public-domain)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Hispana (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
Comunidad de Madrid
Topics
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
hypoxia-inducible factor-1α, renal ischemia-reperfusion injury, acute tubular necrosis, kidney transplantation, proximal tubular epithelial cells, cell survival, renal dysfunction, epithelial cell death
MeSH terms
Adult, Aged, Animals, Cell Survival, Epithelial Cells, Female, Gene Expression Regulation, Humans, Immunohistochemistry, Kidney Tubular Necrosis, Acute, Kidney Tubules, Proximal, Male, Middle Aged, Oxygen, Transcription, Genetic, Transplantation, Homologous, Signal Transduction, Reperfusion Injury, Cell Hypoxia, Kidney Transplantation, Proto-Oncogene Proteins c-akt, Rats, Hypoxia-Inducible Factor 1, alpha Subunit, Young Adult, TOR Serine-Threonine Kinases

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