Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy
Diabetic retinopathy (DR) is a major microvascular complication in diabetics, and its mechanism is not fully understood. Toll-like receptor 4 (TLR4) plays a pivotal role in the maintenance of the inflammatory state during DR, and the deletion of TLR4 eventually alleviates the diabetic inflammatory s...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2014-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/858763 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832562789029249024 |
|---|---|
| author | Hui Wang Haojun Shi Jing Zhang Guoliang Wang Jinxiang Zhang Fagang Jiang Qing Xiao |
| author_facet | Hui Wang Haojun Shi Jing Zhang Guoliang Wang Jinxiang Zhang Fagang Jiang Qing Xiao |
| author_sort | Hui Wang |
| collection | DOAJ |
| description | Diabetic retinopathy (DR) is a major microvascular complication in diabetics, and its mechanism is not fully understood. Toll-like receptor 4 (TLR4) plays a pivotal role in the maintenance of the inflammatory state during DR, and the deletion of TLR4 eventually alleviates the diabetic inflammatory state. To further elucidate the mechanism of DR, we used bone marrow transplantation to establish reciprocal chimeric animals of TLR4 mutant mice and TLR4 WT mice combined with diabetes mellitus (DM) induction by streptozotocin (STZ) treatment to identify the role of TLR4 in different cell types in the development of the proinflammatory state during DR. TLR4 mutation did not block the occurrence of high blood glucose after STZ injection compared with WT mice but did alleviate the progression of DR and alter the expression of the small vessel proliferation-related genes, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α). Grafting bone marrow-derived cells from TLR4 WT mice into TLR4 mutant mice increased the levels of TNF-α, IL-1β, and MIP-2 and increased the damage to the retina. Similarly, VEGF and HIF-1α expression were restored by the bone marrow transplantation. These findings identify an essential role for TLR4 in bone marrow-derived cells contributing to the progression of DR. |
| format | Article |
| id | doaj-art-1806b1e7ba194a7f8847f5c311b0cd6c |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1806b1e7ba194a7f8847f5c311b0cd6c2025-02-03T01:21:40ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/858763858763Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic RetinopathyHui Wang0Haojun Shi1Jing Zhang2Guoliang Wang3Jinxiang Zhang4Fagang Jiang5Qing Xiao6The Department of Medical Genetics, Tongji Medical College Affiliated with Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430022, ChinaRadiology Department, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, ChinaThe Department of Ophthalmology, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, ChinaDepartment of Surgery, University of Pittsburgh Medical Center, NW607 MUH, 3459 Fifth Avenue, Pittsburgh, PA 25213, USAThe Department of Emergency Surgery, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, ChinaThe Department of Ophthalmology, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, ChinaThe Department of Ophthalmology, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, ChinaDiabetic retinopathy (DR) is a major microvascular complication in diabetics, and its mechanism is not fully understood. Toll-like receptor 4 (TLR4) plays a pivotal role in the maintenance of the inflammatory state during DR, and the deletion of TLR4 eventually alleviates the diabetic inflammatory state. To further elucidate the mechanism of DR, we used bone marrow transplantation to establish reciprocal chimeric animals of TLR4 mutant mice and TLR4 WT mice combined with diabetes mellitus (DM) induction by streptozotocin (STZ) treatment to identify the role of TLR4 in different cell types in the development of the proinflammatory state during DR. TLR4 mutation did not block the occurrence of high blood glucose after STZ injection compared with WT mice but did alleviate the progression of DR and alter the expression of the small vessel proliferation-related genes, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α). Grafting bone marrow-derived cells from TLR4 WT mice into TLR4 mutant mice increased the levels of TNF-α, IL-1β, and MIP-2 and increased the damage to the retina. Similarly, VEGF and HIF-1α expression were restored by the bone marrow transplantation. These findings identify an essential role for TLR4 in bone marrow-derived cells contributing to the progression of DR.http://dx.doi.org/10.1155/2014/858763 |
| spellingShingle | Hui Wang Haojun Shi Jing Zhang Guoliang Wang Jinxiang Zhang Fagang Jiang Qing Xiao Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy Mediators of Inflammation |
| title | Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy |
| title_full | Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy |
| title_fullStr | Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy |
| title_full_unstemmed | Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy |
| title_short | Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy |
| title_sort | toll like receptor 4 in bone marrow derived cells contributes to the progression of diabetic retinopathy |
| url | http://dx.doi.org/10.1155/2014/858763 |
| work_keys_str_mv | AT huiwang tolllikereceptor4inbonemarrowderivedcellscontributestotheprogressionofdiabeticretinopathy AT haojunshi tolllikereceptor4inbonemarrowderivedcellscontributestotheprogressionofdiabeticretinopathy AT jingzhang tolllikereceptor4inbonemarrowderivedcellscontributestotheprogressionofdiabeticretinopathy AT guoliangwang tolllikereceptor4inbonemarrowderivedcellscontributestotheprogressionofdiabeticretinopathy AT jinxiangzhang tolllikereceptor4inbonemarrowderivedcellscontributestotheprogressionofdiabeticretinopathy AT fagangjiang tolllikereceptor4inbonemarrowderivedcellscontributestotheprogressionofdiabeticretinopathy AT qingxiao tolllikereceptor4inbonemarrowderivedcellscontributestotheprogressionofdiabeticretinopathy |