miR-142-5p regulates the progression of diabetic retinopathy by targeting IGF1
Xiuming Liu1, Jianchang Li1, Xiaofeng Li1
1Department of Ophthalmology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Abstract:
As one of leading causes of blindness, diabetic retinopathy (DR) is a progressive microvascular complication of diabetes mellitus (DM). Despite significant efforts have been devoted to investigate DR over the years, the molecular mechanisms still remained unclear. Emerging evidences demonstrated that microRNAs (miRNAs) were tightly associated with pathophysiological development of DR. Hence, this study was aimed to illustrate the role and molecular mechanisms of miR-412-5p in progression of DR. Streptozotocin (STZ) treatment in rats and human retinal endothelial cell (HREC) models were used to simulate DR conditions in vivo and in vitro. Hematoxylin-eosin (HE) staining was used to demonstrate the morphology of retinal tissues of rats. Qualitative real-time polymerase chain reaction (qRT-PCR) detected miR-142-5p and vascular endothelial growth factor (VEGF) expression levels. Cell counting kit-8 (CCK8) assay and immunofluorescence (IF) measured the cell proliferation rates. Western blot tested the expression status of IGF1/IGF1R-mediated signaling pathway. Dual-luciferase reporter assays demonstrated the molecular mechanism of miR-142-5p. miR-142-5p level was down-regulated in retinal tissues of DR rats and high glucose (HG)-treated HRECs. Insulin-like growth factor 1 (IGF1) was identified as a direct target of miR-142-5p. The reduced miR-142-5p level enhanced HRECs proliferation via activating IGF/IGF1R-mediated signaling pathway including p-PI3K, p-ERK, p-AKT, and VEGF activation, ultimately giving rise to cell proliferation. Either miR-142-5p overexpression or IGF1 knockdown alleviated the pathological effects on retinal tissues in DR rats. Collectively, miR-142-5p participated in DR development by targeting IGF1/p-IGF1R signaling pathway and VEGF generation. This miR-142-5p/IGF1/VEGF axis provided a novel therapeutic target for DR clinical treatment.
Insights
MicroRNA-412-5p is reduced in diabetic retinopathy (DR), promoting cell proliferation by targeting the IGF1/IGF1R pathway. Restoring miR-412-5p or inhibiting IGF1 could treat DR.
Area of Science:
- Ophthalmology
- Molecular Biology
- Endocrinology
Background:
- Diabetic retinopathy (DR) is a leading cause of blindness and a microvascular complication of diabetes mellitus (DM).
- The precise molecular mechanisms underlying DR pathogenesis remain incompletely understood.
- MicroRNAs (miRNAs) are increasingly recognized for their role in DR development.
Purpose of the Study:
- To investigate the role and molecular mechanisms of miR-412-5p in the progression of diabetic retinopathy (DR).
- To identify potential therapeutic targets for DR based on miRNA regulation.
Main Methods:
- Established in vivo (STZ-induced DR in rats) and in vitro (HG-treated HRECs) models.
- Utilized HE staining, qRT-PCR, CCK8 assays, immunofluorescence, Western blot, and dual-luciferase reporter assays.
- Assessed miR-412-5p, VEGF, and IGF1/IGF1R signaling pathway expression and activity.
Main Results:
- miR-412-5p levels were significantly downregulated in DR rat retinas and HG-treated HRECs.
- Insulin-like growth factor 1 (IGF1) was identified as a direct target of miR-412-5p.
- Reduced miR-412-5p promoted HREC proliferation by activating the IGF1/IGF1R pathway and VEGF, while miR-412-5p overexpression or IGF1 knockdown ameliorated DR pathology.
Conclusions:
- miR-412-5p plays a crucial role in DR progression by regulating the IGF1/IGF1R signaling pathway and VEGF production.
- The identified miR-412-5p/IGF1/VEGF axis represents a novel therapeutic target for diabetic retinopathy.
