The expression and significance of mTORC1 in diabetic retinopathy
Abstract Background To investigate the expression and significance of mechanistic target of rapamycin complex 1(mTORC1) in diabetic retinopathy (DR), and to find new targets and new methods for the treatment of DR. Methods A DR rat model was prepared by general feeding combined with intraperitoneal...
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doaj-8722f7676a4141f09c00983b2c5dc5fc2020-11-25T03:38:38ZengBMCBMC Ophthalmology1471-24152020-07-012011710.1186/s12886-020-01553-3The expression and significance of mTORC1 in diabetic retinopathyYanli Liu0Yarong Zheng1Yekai Zhou2Yi Liu3Mengxuan Xie4Wenjing Meng5Meixia An6The Third Affiliated Hospital of Southern Medical UniversityThe Third Affiliated Hospital of Southern Medical UniversityThe Third Affiliated Hospital of Southern Medical UniversityThe Third Affiliated Hospital of Southern Medical UniversityThe Third Affiliated Hospital of Southern Medical UniversityThe Third Affiliated Hospital of Southern Medical UniversityThe Third Affiliated Hospital of Southern Medical UniversityAbstract Background To investigate the expression and significance of mechanistic target of rapamycin complex 1(mTORC1) in diabetic retinopathy (DR), and to find new targets and new methods for the treatment of DR. Methods A DR rat model was prepared by general feeding combined with intraperitoneal injection of 10% streptozotocin (60 mg/kg). The rats were randomly divided into a control group (NDM group) and a diabetes group (DM group). Three months later, the degrees of retinopathy was determined using hematoxylin and eosin staining, and the levels of p-S6, VEGF, and PEDF proteins were detected by immunohistochemistry and western blotting. Human retinal capillary endothelial cells (HRCECs) were cultured in high glucose (HG) conditions, then treated with rapamycin or transfected with siTSC1.The protein levels of p-S6 were assessed by western blotting. The 5-ethynyl-2′-deoxyuridine assay was used to detect cell proliferation, and the Transwell assay was used to detect cell migration. Results A DM rat model was successfully developed. The expressions of p-S6 and VEGF proteins were significantly increased in the DM group (p < 0.05), and the expression of PEDF protein was significantly decreased compared with the NDM group (p < 0.05). In vitro, the p-S6 protein, as well as cell proliferation and migration, in HG induced HRCECs were increased (p < 0.05) compared with the control (normal glucose) group (p < 0.05). After transfection with siTSC1 to activate mTORC1, the expression of p-S6, as well as cell proliferation and migration, were increased. In contrast, rapamycin decreased p-S6 expression, as well as proliferation and migration, in HG induced HRCECs compared to the control group (p < 0.05). Conclusion mTORC1 plays an important role in DR. After activation, mTORC1 induced expression of the p-S6 protein, regulated the expressions of VEGF and PEDF proteins, and changed the proliferation and migration of endothelial cells. The mTORC1 can therefore be used as a new target,as well as in the treatment of DR.http://link.springer.com/article/10.1186/s12886-020-01553-3Diabetic retinopathymTORC1P-S6VEGFPEDFCell proliferation and migration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yanli Liu Yarong Zheng Yekai Zhou Yi Liu Mengxuan Xie Wenjing Meng Meixia An |
spellingShingle |
Yanli Liu Yarong Zheng Yekai Zhou Yi Liu Mengxuan Xie Wenjing Meng Meixia An The expression and significance of mTORC1 in diabetic retinopathy BMC Ophthalmology Diabetic retinopathy mTORC1 P-S6 VEGF PEDF Cell proliferation and migration |
author_facet |
Yanli Liu Yarong Zheng Yekai Zhou Yi Liu Mengxuan Xie Wenjing Meng Meixia An |
author_sort |
Yanli Liu |
title |
The expression and significance of mTORC1 in diabetic retinopathy |
title_short |
The expression and significance of mTORC1 in diabetic retinopathy |
title_full |
The expression and significance of mTORC1 in diabetic retinopathy |
title_fullStr |
The expression and significance of mTORC1 in diabetic retinopathy |
title_full_unstemmed |
The expression and significance of mTORC1 in diabetic retinopathy |
title_sort |
expression and significance of mtorc1 in diabetic retinopathy |
publisher |
BMC |
series |
BMC Ophthalmology |
issn |
1471-2415 |
publishDate |
2020-07-01 |
description |
Abstract Background To investigate the expression and significance of mechanistic target of rapamycin complex 1(mTORC1) in diabetic retinopathy (DR), and to find new targets and new methods for the treatment of DR. Methods A DR rat model was prepared by general feeding combined with intraperitoneal injection of 10% streptozotocin (60 mg/kg). The rats were randomly divided into a control group (NDM group) and a diabetes group (DM group). Three months later, the degrees of retinopathy was determined using hematoxylin and eosin staining, and the levels of p-S6, VEGF, and PEDF proteins were detected by immunohistochemistry and western blotting. Human retinal capillary endothelial cells (HRCECs) were cultured in high glucose (HG) conditions, then treated with rapamycin or transfected with siTSC1.The protein levels of p-S6 were assessed by western blotting. The 5-ethynyl-2′-deoxyuridine assay was used to detect cell proliferation, and the Transwell assay was used to detect cell migration. Results A DM rat model was successfully developed. The expressions of p-S6 and VEGF proteins were significantly increased in the DM group (p < 0.05), and the expression of PEDF protein was significantly decreased compared with the NDM group (p < 0.05). In vitro, the p-S6 protein, as well as cell proliferation and migration, in HG induced HRCECs were increased (p < 0.05) compared with the control (normal glucose) group (p < 0.05). After transfection with siTSC1 to activate mTORC1, the expression of p-S6, as well as cell proliferation and migration, were increased. In contrast, rapamycin decreased p-S6 expression, as well as proliferation and migration, in HG induced HRCECs compared to the control group (p < 0.05). Conclusion mTORC1 plays an important role in DR. After activation, mTORC1 induced expression of the p-S6 protein, regulated the expressions of VEGF and PEDF proteins, and changed the proliferation and migration of endothelial cells. The mTORC1 can therefore be used as a new target,as well as in the treatment of DR. |
topic |
Diabetic retinopathy mTORC1 P-S6 VEGF PEDF Cell proliferation and migration |
url |
http://link.springer.com/article/10.1186/s12886-020-01553-3 |
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