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

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, del Peso L, de Landázuri MO, Liaño F, Selgas R, Sanchez-Tomero JA, García-Bermejo ML - PLoS ONE (2012)

Bottom Line: Both inductions lead to gene expression in vitro and in vivo.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.

View Article: PubMed Central - PubMed

Affiliation: Department of System Disorders and Cancer, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Alcalá University, Madrid, Spain.

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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Related in: MedlinePlus

HIF-1 α is induced unexpectedly during reperfusion in rat kidney, with normal oxygen levels in renal parenchyma.(a) Immunohistochemitry to determine HIF-1 α expression in paraffin-embedded renal tissue sections from SD rats during I/R. Ischemia of 45 min and different times of reperfusion: 24 hours or 3, 5 or 7 days (R-24h, R-3d, R-5d, R-7d). HIF-1 α is detected in the nucleus of proximal tubule cells after ischemia and in reperfusion (3-5-7days). Magnification: ×400 (b) Immunostaining for pimonidazol-protein and HIF-1α adducts in renal tissue sections of rats during I/R. Ischemia of 45 min and 5 days of reperfusion. Notice positive pimonidazole immunostaining exclusively after ischemia. Magnification: ×200.
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pone-0033258-g004: HIF-1 α is induced unexpectedly during reperfusion in rat kidney, with normal oxygen levels in renal parenchyma.(a) Immunohistochemitry to determine HIF-1 α expression in paraffin-embedded renal tissue sections from SD rats during I/R. Ischemia of 45 min and different times of reperfusion: 24 hours or 3, 5 or 7 days (R-24h, R-3d, R-5d, R-7d). HIF-1 α is detected in the nucleus of proximal tubule cells after ischemia and in reperfusion (3-5-7days). Magnification: ×400 (b) Immunostaining for pimonidazol-protein and HIF-1α adducts in renal tissue sections of rats during I/R. Ischemia of 45 min and 5 days of reperfusion. Notice positive pimonidazole immunostaining exclusively after ischemia. Magnification: ×200.

Mentions: Immunohistochemistry in renal tissue demonstrated HIF-1 α expression in the nucleus of proximal tubule cells after ischemia, and, unexpectedly during reperfusion, between days 3 and 7 (figure 4A). As expected, pimonidazole staining revealed tissue hypoxia after ischemia, but it was negative at 5 days of reperfusion, indicating that tissue oxygen levels are not compromised at this moment even though HIF-1 α accumulates (figure 4B).


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

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, del Peso L, de Landázuri MO, Liaño F, Selgas R, Sanchez-Tomero JA, García-Bermejo ML - PLoS ONE (2012)

HIF-1 α is induced unexpectedly during reperfusion in rat kidney, with normal oxygen levels in renal parenchyma.(a) Immunohistochemitry to determine HIF-1 α expression in paraffin-embedded renal tissue sections from SD rats during I/R. Ischemia of 45 min and different times of reperfusion: 24 hours or 3, 5 or 7 days (R-24h, R-3d, R-5d, R-7d). HIF-1 α is detected in the nucleus of proximal tubule cells after ischemia and in reperfusion (3-5-7days). Magnification: ×400 (b) Immunostaining for pimonidazol-protein and HIF-1α adducts in renal tissue sections of rats during I/R. Ischemia of 45 min and 5 days of reperfusion. Notice positive pimonidazole immunostaining exclusively after ischemia. Magnification: ×200.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303832&req=5

pone-0033258-g004: HIF-1 α is induced unexpectedly during reperfusion in rat kidney, with normal oxygen levels in renal parenchyma.(a) Immunohistochemitry to determine HIF-1 α expression in paraffin-embedded renal tissue sections from SD rats during I/R. Ischemia of 45 min and different times of reperfusion: 24 hours or 3, 5 or 7 days (R-24h, R-3d, R-5d, R-7d). HIF-1 α is detected in the nucleus of proximal tubule cells after ischemia and in reperfusion (3-5-7days). Magnification: ×400 (b) Immunostaining for pimonidazol-protein and HIF-1α adducts in renal tissue sections of rats during I/R. Ischemia of 45 min and 5 days of reperfusion. Notice positive pimonidazole immunostaining exclusively after ischemia. Magnification: ×200.
Mentions: Immunohistochemistry in renal tissue demonstrated HIF-1 α expression in the nucleus of proximal tubule cells after ischemia, and, unexpectedly during reperfusion, between days 3 and 7 (figure 4A). As expected, pimonidazole staining revealed tissue hypoxia after ischemia, but it was negative at 5 days of reperfusion, indicating that tissue oxygen levels are not compromised at this moment even though HIF-1 α accumulates (figure 4B).

Bottom Line: Both inductions lead to gene expression in vitro and in vivo.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.

View Article: PubMed Central - PubMed

Affiliation: Department of System Disorders and Cancer, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Alcalá University, Madrid, Spain.

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.

Show MeSH
Related in: MedlinePlus