Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin
Mannan-binding lectin (MBL) has been reported to be involved in the pathophysiology of diabetic nephropathy. MBL is a pattern-recognition molecule of the innate immune system that initiates the lectin pathway of the complement system upon recognition of evolutionary conserved pathogen-associated mol...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2017/6368780 |
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| _version_ | 1832550986775789568 |
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| author | Esben Axelgaard Jakob Appel Østergaard Steffen Thiel Troels Krarup Hansen |
| author_facet | Esben Axelgaard Jakob Appel Østergaard Steffen Thiel Troels Krarup Hansen |
| author_sort | Esben Axelgaard |
| collection | DOAJ |
| description | Mannan-binding lectin (MBL) has been reported to be involved in the pathophysiology of diabetic nephropathy. MBL is a pattern-recognition molecule of the innate immune system that initiates the lectin pathway of the complement system upon recognition of evolutionary conserved pathogen-associated molecular patterns or to altered self-tissue. Our group have previously shown direct effects of MBL on diabetes-induced kidney damage, and we hypothesized that MBL may cause autoactivation of the complement system via binding to neoepitopes induced by hyperglycemia. In the present study, we induced diabetes in MBL knockout mice and in wild type C57BL/6J mice by low-dose streptozotocin injection and measured blood glucose and urine albumin-to-creatinine ratio to monitor development of diabetes. After 24 weeks, fluorescently labelled recombinant MBL was injected intravenously in diabetic MBL knockout mice after which the distribution was investigated using in vivo fluorescence imaging. Mice were subjected to in vivo and ex vivo imaging 24 hours after injection. MBL was found to accumulate in the kidneys of diabetic mice as compared to healthy control mice (p<0.0001). These findings support the hypothesis of a significant role of MBL and the complement system in the pathophysiology of diabetic nephropathy. |
| format | Article |
| id | doaj-art-83a682dc8575428dbf7816a590400750 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-83a682dc8575428dbf7816a5904007502025-02-03T06:05:22ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/63687806368780Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding LectinEsben Axelgaard0Jakob Appel Østergaard1Steffen Thiel2Troels Krarup Hansen3Department of Biomedicine, Faculty of Health Sciences, Aarhus University, Wilhelm Meyer’s Allé 4, Aarhus C, Aarhus, DenmarkDepartment of Endocrinology and Internal Medicine, Aarhus University Hospital and Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Faculty of Health Sciences, Aarhus University, Wilhelm Meyer’s Allé 4, Aarhus C, Aarhus, DenmarkDepartment of Endocrinology and Internal Medicine, Aarhus University Hospital and Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, DenmarkMannan-binding lectin (MBL) has been reported to be involved in the pathophysiology of diabetic nephropathy. MBL is a pattern-recognition molecule of the innate immune system that initiates the lectin pathway of the complement system upon recognition of evolutionary conserved pathogen-associated molecular patterns or to altered self-tissue. Our group have previously shown direct effects of MBL on diabetes-induced kidney damage, and we hypothesized that MBL may cause autoactivation of the complement system via binding to neoepitopes induced by hyperglycemia. In the present study, we induced diabetes in MBL knockout mice and in wild type C57BL/6J mice by low-dose streptozotocin injection and measured blood glucose and urine albumin-to-creatinine ratio to monitor development of diabetes. After 24 weeks, fluorescently labelled recombinant MBL was injected intravenously in diabetic MBL knockout mice after which the distribution was investigated using in vivo fluorescence imaging. Mice were subjected to in vivo and ex vivo imaging 24 hours after injection. MBL was found to accumulate in the kidneys of diabetic mice as compared to healthy control mice (p<0.0001). These findings support the hypothesis of a significant role of MBL and the complement system in the pathophysiology of diabetic nephropathy.http://dx.doi.org/10.1155/2017/6368780 |
| spellingShingle | Esben Axelgaard Jakob Appel Østergaard Steffen Thiel Troels Krarup Hansen Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin Journal of Diabetes Research |
| title | Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin |
| title_full | Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin |
| title_fullStr | Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin |
| title_full_unstemmed | Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin |
| title_short | Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin |
| title_sort | diabetes is associated with increased autoreactivity of mannan binding lectin |
| url | http://dx.doi.org/10.1155/2017/6368780 |
| work_keys_str_mv | AT esbenaxelgaard diabetesisassociatedwithincreasedautoreactivityofmannanbindinglectin AT jakobappeløstergaard diabetesisassociatedwithincreasedautoreactivityofmannanbindinglectin AT steffenthiel diabetesisassociatedwithincreasedautoreactivityofmannanbindinglectin AT troelskraruphansen diabetesisassociatedwithincreasedautoreactivityofmannanbindinglectin |