microRNA-199a-5p regulates epithelial-to-mesenchymal transition in diabetic cataract by targeting SP1 gene

Abstract

Background As a common ocular complication of diabetes mellitus, diabetic cataract is becoming a leading cause of visual impairment. The progression of diabetic cataract progression involves epithelial-to-mesenchymal transition (EMT), the precise role of which remains to be investigated. As microRNAs (miRNAs) are suggested to be involved in the pathogenesis of many diseases, identification of aberrantly expressed miRNAs in diabetic lens epithelial cells (LECs) and their targets may provide insights into our understanding of diabetic cataract and potential therapeutic targets. Methods Diabetic cataract capsules and LECs exposed to high glucose (25 mmol/L, 1–5 days) were used to mimic the model. Quantitative RT-PCR was performed to evaluate the differential expression of miRNA. Dual luciferase reporter assay was used to identify the binding target of miR-199a-5p. The expression of EMT-associated proteins was determined by immunofluorescence and Western blot analysis. Results Our results showed the differential expression of miR-9, -16, -22, -199a and -204. MiR-199a was downregulated in diabetic cataract capsule and hyperglycemia-conditioned human LECs. Specific protein 1 could be directly targeted and regulated by miR-199a in LECs and inhibit EMT in diabetic LECs. Conclusion Our findings implied miR-199a could be a therapeutic target by regulating SP1 directly to affect EMT in diabetic cataract and provided novel insights into the pathogenesis of diabetic cataract.

The interaction between autophagy and the epithelial-mesenchymal transition mediated by NICD/ULK1 is involved in the formation of diabetic cataracts

“…The correlation between the EMT of LECs and diabetic cataracts has been reported (Zhang et al 2017; Du et al 2017 ; Liu et al 2020 ). We have also confirmed that high-glucose stimulation induces the EMT of LECs in vitro (Han et al 2018 ; Li et al 2020 ; Ye et al 2020 ).…”

“…Autophagy is essential for maintaining the homeostasis of cells, tissues and organs (Dikic and Elazar 2018 ), especially in the eye, including the cornea, retina, and lens (Chai et al 2016 ). Impairment of autophagy flux in LECs and fiber cells may result in the formation of congenital cataracts, age-related cataracts, and diabetic cataracts (Morishita et al 2013 ; Liu et al 2020 ; Andley and Goldman 2016 ). In the present study, autophagic activity was attenuated both in LECs of diabetic rats and in HLE-B3 cells stimulated with high glucose concentrations, consistent with the findings of many other studies (Chen et al 2021 ; Li et al 2020 ).…”

“…In the present study, autophagic activity was attenuated both in LECs of diabetic rats and in HLE-B3 cells stimulated with high glucose concentrations, consistent with the findings of many other studies (Chen et al 2021 ; Li et al 2020 ). However, Liu has showed that autophagy changes from activation at the early stage to subsequent inhibition in the LECs of mice under high-glucose conditions (Liu et al 2020 ). The possible explanations for this discrepancy are described below.…”

“…The presence of autophagic vesicles containing mitochondria in LECs, immature lens fiber cells and during the early stages of lens fiber cell differentiation has been documented, indicating that autophagy occurs throughout the development of the lens (Costello et al 2013 ). Numerous studies have reported that dysregulation of autophagy is involved in the formation of different types of cataracts, such as congenital cataracts (Wignes et al 2013 ; Chen et al 2011 ), age-related cataracts (Morishita et al 2013 ; Zhou et al 2016 ), and diabetic cataracts (Liu et al 2020 ; Chen et al 2021 ). We speculate that autophagy is activated in normal LECs and that the loss of autophagy may result in alterations in lens development, loss of lens homeostasis and cataract formation.…”

A Network Pharmacology Study on the Molecular Mechanism of Protocatechualdehyde in the Treatment of Diabetic Cataract

“…of sorbitol, galactitol and advanced glycation end products (AGEs), and oxidative stress damage activated by reactive oxygen species (ROS). [21][22][23][24] At present, the effective treatment for various types of cataracts is still surgery, and there is still no medicine that can effectively inhibit or delay the occurrence and development of DC. The reason is that the purification methods of the drugs studied in these experiments are not uniform, or the way of action of drugs on diabetic cataract is relatively single, so it may be weak for the drugs on the effect of diabetic cataract with complex pathogenesis in actual clinical conditions.…”