microRNA-199a-5p regulates epithelial-to-mesenchymal transition in diabetic cataract by targeting SP1 gene
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Molecular Medicine
Open Access
RESEARCH ARTICLE
microRNA‑199a‑5p regulates epithelial‑to‑mesenchymal transition in diabetic cataract by targeting SP1 gene Xin Liu1†, Qiaoyun Gong1,2†, Longfei Yang3, Min Liu1, Lingzhi Niu1 and Lufei Wang1*
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. Keywords: Diabetic cataract, MiR-199a-5p, Epithelial-to-mesenchymal transition, Specific protein 1 Background Diabetes mellitus (DM) is a kind of endocrine diseases that seriously endanger human health and the incidence is increasing globally. As the common ocular complication of DM, diabetic cataract, as well as diabetic retinopathy, becomes the leading cause of visual impairment for the incidence and progression is *Correspondence: [email protected] † Xin Liu and Qiaoyun Gong contributed equally in this work † Xin Liu and Qiaoyun Gong are co-first authors 1 Eye Center, The Second Hospital of Jilin University, #218 Ziqiang Street, Changchun, Jilin, China Full list of author information is available at the end of the article
increasing in patients with DM (Pollreisz and SchmidtErfurth 2010). Diabetic cataract often manifests earlier and severer than the age-related cataract (ARC), in which hyperglycemia seems to play a promoting role, including activation of the aldose reductase (AR) receptor, accumulation of sorbitol and galactositol and advanced glycation end-products(AGE), and oxidative stress damage actived by reactive oxygen species (ROS) in LECs (Oishi et al. (2006); Varma et al. 2012; Martinez and Iongh 2010; Peppa and Vlassara 2005). The pathogenesis of diabetic cataract is a multifactorial p
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