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The expression and significance of mTORC1 in diabetic retinopathy
Yanli Liu1,2, Yarong Zheng1,2, Yekai Zhou1,2
1The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510515, China.
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.
Insights
Mechanistic target of rapamycin complex 1 (mTORC1) activation increases p-S6, VEGF, and PEDF protein levels in diabetic retinopathy (DR). Targeting mTORC1 offers a new therapeutic strategy for DR treatment.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Diabetic retinopathy (DR) is a complication of diabetes affecting the eyes.
- Mechanistic target of rapamycin complex 1 (mTORC1) is implicated in various cellular processes.
- Understanding mTORC1's role in DR is crucial for developing new treatments.
Purpose of the Study:
- To investigate the expression and significance of mTORC1 in DR.
- To identify potential new therapeutic targets and methods for DR treatment.
Main Methods:
- A diabetic rat model was established using streptozotocin.
- Retinopathy was assessed via hematoxylin and eosin staining.
- Protein levels (p-S6, VEGF, PEDF) were measured using immunohistochemistry and western blotting.
- Human retinal capillary endothelial cells (HRCECs) were cultured under high glucose conditions and treated with rapamycin or transfected with siTSC1.
- Cell proliferation and migration were evaluated using EDU and Transwell assays.
Main Results:
- Diabetic rats showed increased p-S6 and VEGF, and decreased PEDF expression compared to controls.
- High glucose induced increased p-S6, proliferation, and migration in HRCECs.
- Activating mTORC1 (siTSC1) further increased p-S6, proliferation, and migration.
- Rapamycin treatment reduced p-S6, proliferation, and migration in high glucose conditions.
Conclusions:
- mTORC1 plays a significant role in the pathogenesis of diabetic retinopathy.
- Activated mTORC1 influences p-S6, VEGF, and PEDF protein expression.
- mTORC1 modulates endothelial cell proliferation and migration in DR.
- mTORC1 represents a promising therapeutic target for diabetic retinopathy.
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