Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with potential severe consequences. Its pathogenesis involves hyperglycemia-linked mechanisms, which may include changes in the expression of neurotrophic growth factors. We analyzed the expression of 29 factors potentially re...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2018/2309108 |
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| author | František Saudek Monika Cahová Terezie Havrdová Klára Zacharovová Helena Daňková Luděk Voska Věra Lánská Nurcan Üçeyler Claudia Sommer |
| author_facet | František Saudek Monika Cahová Terezie Havrdová Klára Zacharovová Helena Daňková Luděk Voska Věra Lánská Nurcan Üçeyler Claudia Sommer |
| author_sort | František Saudek |
| collection | DOAJ |
| description | Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with potential severe consequences. Its pathogenesis involves hyperglycemia-linked mechanisms, which may include changes in the expression of neurotrophic growth factors. We analyzed the expression of 29 factors potentially related to nerve degeneration and regeneration in skin biopsies from 13 type 1 diabetic pancreas and kidney recipients with severe DPN including severe depletion of intraepidermal nerve fibers (IENF) in lower limb skin biopsies (group Tx1 1st examination). The investigation was repeated after a median 28-month period of normoglycemia achieved by pancreas transplantation (group Tx1 2nd examination). The same tests were performed in 13 stable normoglycemic pancreas and kidney recipients 6–12 years posttransplantation (group Tx2), in 12 matched healthy controls (group HC), and in 12 type 1 diabetic subjects without severe DPN (group DM). Compared to DM and HC groups, we found a significantly higher (p < 0.05–0.001) expression of NGF (nerve growth factor), NGFR (NGF receptor), NTRK1 (neurotrophic receptor tyrosine kinase 1), GDNF (glial cell-derived neurotrophic factor), GFRA1 (GDNF family receptor alpha 1), and GFAP (glial fibrillary acidic protein) in both transplant groups (Tx1 and Tx2). Enhanced expression of these factors was not normalized following the median 28-month period of normoglycemia (Tx1 2nd examination) and negatively correlated with IENF density and with electrophysiological indices of DPN (vibration perception threshold, electromyography, and autonomic tests). In contrast to our expectation, the expression of most of 29 selected factors related to neural regeneration was comparable in subjects with severe peripheral nerve fiber depletion and healthy controls and the expression of six factors was significantly upregulated. These findings may be important for better understanding the pathophysiology of nerve regeneration and for the development of intervention strategies. |
| format | Article |
| id | doaj-art-d7737eea0f7f41b09404903f36496b7f |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-d7737eea0f7f41b09404903f36496b7f2025-02-03T07:24:48ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/23091082309108Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney TransplantationFrantišek Saudek0Monika Cahová1Terezie Havrdová2Klára Zacharovová3Helena Daňková4Luděk Voska5Věra Lánská6Nurcan Üçeyler7Claudia Sommer8Diabetes Center, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCenter for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicDiabetes Center, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCenter for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCenter for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicClinical and Transplant Pathology Department, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicDepartment of Statistics, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicUniversity Hospital of Würzburg, Department of Neurology, 97080 Würzburg, GermanyUniversity Hospital of Würzburg, Department of Neurology, 97080 Würzburg, GermanyDiabetic peripheral neuropathy (DPN) is a common complication of diabetes with potential severe consequences. Its pathogenesis involves hyperglycemia-linked mechanisms, which may include changes in the expression of neurotrophic growth factors. We analyzed the expression of 29 factors potentially related to nerve degeneration and regeneration in skin biopsies from 13 type 1 diabetic pancreas and kidney recipients with severe DPN including severe depletion of intraepidermal nerve fibers (IENF) in lower limb skin biopsies (group Tx1 1st examination). The investigation was repeated after a median 28-month period of normoglycemia achieved by pancreas transplantation (group Tx1 2nd examination). The same tests were performed in 13 stable normoglycemic pancreas and kidney recipients 6–12 years posttransplantation (group Tx2), in 12 matched healthy controls (group HC), and in 12 type 1 diabetic subjects without severe DPN (group DM). Compared to DM and HC groups, we found a significantly higher (p < 0.05–0.001) expression of NGF (nerve growth factor), NGFR (NGF receptor), NTRK1 (neurotrophic receptor tyrosine kinase 1), GDNF (glial cell-derived neurotrophic factor), GFRA1 (GDNF family receptor alpha 1), and GFAP (glial fibrillary acidic protein) in both transplant groups (Tx1 and Tx2). Enhanced expression of these factors was not normalized following the median 28-month period of normoglycemia (Tx1 2nd examination) and negatively correlated with IENF density and with electrophysiological indices of DPN (vibration perception threshold, electromyography, and autonomic tests). In contrast to our expectation, the expression of most of 29 selected factors related to neural regeneration was comparable in subjects with severe peripheral nerve fiber depletion and healthy controls and the expression of six factors was significantly upregulated. These findings may be important for better understanding the pathophysiology of nerve regeneration and for the development of intervention strategies.http://dx.doi.org/10.1155/2018/2309108 |
| spellingShingle | František Saudek Monika Cahová Terezie Havrdová Klára Zacharovová Helena Daňková Luděk Voska Věra Lánská Nurcan Üçeyler Claudia Sommer Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation Journal of Diabetes Research |
| title | Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation |
| title_full | Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation |
| title_fullStr | Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation |
| title_full_unstemmed | Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation |
| title_short | Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation |
| title_sort | preserved expression of skin neurotrophic factors in advanced diabetic neuropathy does not lead to neural regeneration despite pancreas and kidney transplantation |
| url | http://dx.doi.org/10.1155/2018/2309108 |
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