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RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice

Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE...

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Autores principales: Juranek, Judyta K., Geddis, Matthew S., Song, Fei, Zhang, Jinghua, Garcia, Jose, Rosario, Rosa, Yan, Shi Fang, Brannagan, Thomas H., Schmidt, Ann Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581233/
https://www.ncbi.nlm.nih.gov/pubmed/23172920
http://dx.doi.org/10.2337/db12-0632
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author Juranek, Judyta K.
Geddis, Matthew S.
Song, Fei
Zhang, Jinghua
Garcia, Jose
Rosario, Rosa
Yan, Shi Fang
Brannagan, Thomas H.
Schmidt, Ann Marie
author_facet Juranek, Judyta K.
Geddis, Matthew S.
Song, Fei
Zhang, Jinghua
Garcia, Jose
Rosario, Rosa
Yan, Shi Fang
Brannagan, Thomas H.
Schmidt, Ann Marie
author_sort Juranek, Judyta K.
collection PubMed
description Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses effective axonal regeneration in superimposed acute peripheral nerve injury attributable to tissue-damaging inflammatory responses. We report that deletion of RAGE, particularly in diabetic mice, resulted in significantly higher myelinated fiber densities and conduction velocities consequent to acute sciatic nerve crush compared with wild-type control animals. Consistent with key roles for RAGE-dependent inflammation, reconstitution of diabetic wild-type mice with RAGE-null versus wild-type bone marrow resulted in significantly improved axonal regeneration and restoration of function. Diabetic RAGE-null mice displayed higher numbers of invading macrophages in the nerve segments postcrush compared with wild-type animals, and these macrophages in diabetic RAGE-null mice displayed greater M2 polarization. In vitro, treatment of wild-type bone marrow–derived macrophages with advanced glycation end products (AGEs), which accumulate in diabetic nerve tissue, increased M1 and decreased M2 gene expression in a RAGE-dependent manner. Blockade of RAGE may be beneficial in the acute complications of diabetic neuropathy, at least in part, via upregulation of regeneration signals.
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spelling pubmed-35812332014-03-01 RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice Juranek, Judyta K. Geddis, Matthew S. Song, Fei Zhang, Jinghua Garcia, Jose Rosario, Rosa Yan, Shi Fang Brannagan, Thomas H. Schmidt, Ann Marie Diabetes Complications Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses effective axonal regeneration in superimposed acute peripheral nerve injury attributable to tissue-damaging inflammatory responses. We report that deletion of RAGE, particularly in diabetic mice, resulted in significantly higher myelinated fiber densities and conduction velocities consequent to acute sciatic nerve crush compared with wild-type control animals. Consistent with key roles for RAGE-dependent inflammation, reconstitution of diabetic wild-type mice with RAGE-null versus wild-type bone marrow resulted in significantly improved axonal regeneration and restoration of function. Diabetic RAGE-null mice displayed higher numbers of invading macrophages in the nerve segments postcrush compared with wild-type animals, and these macrophages in diabetic RAGE-null mice displayed greater M2 polarization. In vitro, treatment of wild-type bone marrow–derived macrophages with advanced glycation end products (AGEs), which accumulate in diabetic nerve tissue, increased M1 and decreased M2 gene expression in a RAGE-dependent manner. Blockade of RAGE may be beneficial in the acute complications of diabetic neuropathy, at least in part, via upregulation of regeneration signals. American Diabetes Association 2013-03 2013-02-14 /pmc/articles/PMC3581233/ /pubmed/23172920 http://dx.doi.org/10.2337/db12-0632 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Complications
Juranek, Judyta K.
Geddis, Matthew S.
Song, Fei
Zhang, Jinghua
Garcia, Jose
Rosario, Rosa
Yan, Shi Fang
Brannagan, Thomas H.
Schmidt, Ann Marie
RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice
title RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice
title_full RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice
title_fullStr RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice
title_full_unstemmed RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice
title_short RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice
title_sort rage deficiency improves postinjury sciatic nerve regeneration in type 1 diabetic mice
topic Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581233/
https://www.ncbi.nlm.nih.gov/pubmed/23172920
http://dx.doi.org/10.2337/db12-0632
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