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Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion
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| Zeitschriftentitel: | American Journal of Physiology-Renal Physiology |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | American Journal of Physiology-Renal Physiology, 316, 2019, 6, S. F1124-F1132 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Physiological Society
|
| Schlagwörter: |
| author_facet |
Baisantry, Arpita Berkenkamp, Birgit Rong, Song Bhayadia, Raj Sörensen-Zender, Inga Schmitt, Roland Melk, Anette Baisantry, Arpita Berkenkamp, Birgit Rong, Song Bhayadia, Raj Sörensen-Zender, Inga Schmitt, Roland Melk, Anette |
|---|---|
| author |
Baisantry, Arpita Berkenkamp, Birgit Rong, Song Bhayadia, Raj Sörensen-Zender, Inga Schmitt, Roland Melk, Anette |
| spellingShingle |
Baisantry, Arpita Berkenkamp, Birgit Rong, Song Bhayadia, Raj Sörensen-Zender, Inga Schmitt, Roland Melk, Anette American Journal of Physiology-Renal Physiology Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion Physiology |
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baisantry, arpita |
| spelling |
Baisantry, Arpita Berkenkamp, Birgit Rong, Song Bhayadia, Raj Sörensen-Zender, Inga Schmitt, Roland Melk, Anette 1931-857X 1522-1466 American Physiological Society Physiology http://dx.doi.org/10.1152/ajprenal.00333.2018 <jats:p> Inhibition of p53 has been shown to be an efficient strategy for ameliorating kidney ischemia-reperfusion (I/R) injury in experimental models. The therapeutic value of p53 siRNA-based inhibition for I/R in renal transplantation is currently being evaluated in clinical studies. While the major rationale for these studies is the suppression of proapoptotic properties, there are more equally important injury response pathways regulated by p53. A p53-dependent pathway shown to be crucial for renal long-term outcome is cellular senescence. In this study, we tested the hypothesis that p53 siRNA reduces I/R-induced senescence and thereby improves kidney outcome. By comparing the impact of different treatment durations in a mouse model of renal I/R, we found that repetitive administration of p53 siRNA during the first 14 days after I/R reduced the senescence load and ameliorated the postischemic phenotype. Prolonged application of p53 siRNA over a 26-day period after I/R, however, did not provide any additional benefit for senescence reduction but reversed some of the renoprotective effects of the early treatment. These data suggest a time-dependent role of p53 activity supporting the current therapeutic concept of a short-term inhibition, while advocating against a prolonged treatment after I/R. </jats:p> Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion American Journal of Physiology-Renal Physiology |
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| title |
Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_unstemmed |
Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_full |
Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_fullStr |
Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_full_unstemmed |
Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_short |
Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_sort |
time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| topic |
Physiology |
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http://dx.doi.org/10.1152/ajprenal.00333.2018 |
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2019 |
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F1124-F1132 |
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<jats:p> Inhibition of p53 has been shown to be an efficient strategy for ameliorating kidney ischemia-reperfusion (I/R) injury in experimental models. The therapeutic value of p53 siRNA-based inhibition for I/R in renal transplantation is currently being evaluated in clinical studies. While the major rationale for these studies is the suppression of proapoptotic properties, there are more equally important injury response pathways regulated by p53. A p53-dependent pathway shown to be crucial for renal long-term outcome is cellular senescence. In this study, we tested the hypothesis that p53 siRNA reduces I/R-induced senescence and thereby improves kidney outcome. By comparing the impact of different treatment durations in a mouse model of renal I/R, we found that repetitive administration of p53 siRNA during the first 14 days after I/R reduced the senescence load and ameliorated the postischemic phenotype. Prolonged application of p53 siRNA over a 26-day period after I/R, however, did not provide any additional benefit for senescence reduction but reversed some of the renoprotective effects of the early treatment. These data suggest a time-dependent role of p53 activity supporting the current therapeutic concept of a short-term inhibition, while advocating against a prolonged treatment after I/R. </jats:p> |
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| author | Baisantry, Arpita, Berkenkamp, Birgit, Rong, Song, Bhayadia, Raj, Sörensen-Zender, Inga, Schmitt, Roland, Melk, Anette |
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| description | <jats:p> Inhibition of p53 has been shown to be an efficient strategy for ameliorating kidney ischemia-reperfusion (I/R) injury in experimental models. The therapeutic value of p53 siRNA-based inhibition for I/R in renal transplantation is currently being evaluated in clinical studies. While the major rationale for these studies is the suppression of proapoptotic properties, there are more equally important injury response pathways regulated by p53. A p53-dependent pathway shown to be crucial for renal long-term outcome is cellular senescence. In this study, we tested the hypothesis that p53 siRNA reduces I/R-induced senescence and thereby improves kidney outcome. By comparing the impact of different treatment durations in a mouse model of renal I/R, we found that repetitive administration of p53 siRNA during the first 14 days after I/R reduced the senescence load and ameliorated the postischemic phenotype. Prolonged application of p53 siRNA over a 26-day period after I/R, however, did not provide any additional benefit for senescence reduction but reversed some of the renoprotective effects of the early treatment. These data suggest a time-dependent role of p53 activity supporting the current therapeutic concept of a short-term inhibition, while advocating against a prolonged treatment after I/R. </jats:p> |
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| spelling | Baisantry, Arpita Berkenkamp, Birgit Rong, Song Bhayadia, Raj Sörensen-Zender, Inga Schmitt, Roland Melk, Anette 1931-857X 1522-1466 American Physiological Society Physiology http://dx.doi.org/10.1152/ajprenal.00333.2018 <jats:p> Inhibition of p53 has been shown to be an efficient strategy for ameliorating kidney ischemia-reperfusion (I/R) injury in experimental models. The therapeutic value of p53 siRNA-based inhibition for I/R in renal transplantation is currently being evaluated in clinical studies. While the major rationale for these studies is the suppression of proapoptotic properties, there are more equally important injury response pathways regulated by p53. A p53-dependent pathway shown to be crucial for renal long-term outcome is cellular senescence. In this study, we tested the hypothesis that p53 siRNA reduces I/R-induced senescence and thereby improves kidney outcome. By comparing the impact of different treatment durations in a mouse model of renal I/R, we found that repetitive administration of p53 siRNA during the first 14 days after I/R reduced the senescence load and ameliorated the postischemic phenotype. Prolonged application of p53 siRNA over a 26-day period after I/R, however, did not provide any additional benefit for senescence reduction but reversed some of the renoprotective effects of the early treatment. These data suggest a time-dependent role of p53 activity supporting the current therapeutic concept of a short-term inhibition, while advocating against a prolonged treatment after I/R. </jats:p> Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion American Journal of Physiology-Renal Physiology |
| spellingShingle | Baisantry, Arpita, Berkenkamp, Birgit, Rong, Song, Bhayadia, Raj, Sörensen-Zender, Inga, Schmitt, Roland, Melk, Anette, American Journal of Physiology-Renal Physiology, Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion, Physiology |
| title | Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_full | Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_fullStr | Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_full_unstemmed | Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_short | Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_sort | time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| title_unstemmed | Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion |
| topic | Physiology |
| url | http://dx.doi.org/10.1152/ajprenal.00333.2018 |