Up‐regulation of miR‐192‐5p inhibits the ELAVL1/PI3Kδ axis and attenuates microvascular endothelial cell proliferation, migration and angiogenesis in diabetic retinopathy
Abstract:Background: Diabetic retinopathy (DR) is a common complication of diabetes and a sight threaten among adults. MicroRNAs (miRNAs) serve a key role in DR progression. However, the role and mechanism of miR-192-5p in DR remain unclear. We aim to investigate the effect of miR-192-5p on cell proliferation, migration and angiogenesis in DR. Methods: The expressions of miR-192-5p, ELAVL1 and PI3Kδ in DR samples and human retinal microvascular endothelial cells (HRMECs) were assessed using RT-qPCR. ELAVL1 and PI3Kδ pr… Show more
“…Several key pathways were noted to be regulated by these miRs ( Figure 2 , A) Review of the literature revealed 3 miRs (miR-92, -103 and -192) with confirmed roles in cellular growth and proliferation. 33 , 34 , 35 Figure 2 MicroRNA array Several microRNA-regulated pathways were noted ( A ). MicroRNAs were assessed and 3 microRNAs (mir-92, -103, and -192) in placenta previa ( B ) were exclusively expressed in PAS specimens ( C ) in this cohort.…”
“…Several key pathways were noted to be regulated by these miRs ( Figure 2 , A) Review of the literature revealed 3 miRs (miR-92, -103 and -192) with confirmed roles in cellular growth and proliferation. 33 , 34 , 35 Figure 2 MicroRNA array Several microRNA-regulated pathways were noted ( A ). MicroRNAs were assessed and 3 microRNAs (mir-92, -103, and -192) in placenta previa ( B ) were exclusively expressed in PAS specimens ( C ) in this cohort.…”
“…Additionally, IGF-1 promotes the production of nitric oxide by endothelial and vascular smooth muscle cells, thereby safeguarding vascular function (Higashi et al 2019) Previous studies have shown that miR-192-5p can prevent hypertension by inhibiting the expression of Atp1b1 (Baker et al 2019). Additionally, high expression of miR-192-5p has been found to inhibit microvascular endothelial cell proliferation, migration, and angiogenesis, thereby playing a protective role in small blood vessels (Fu et al 2023). In our current study, we observed high expression of miR-192-5p in the blood of patients with EH, suggesting that this may be a regulatory mechanism within the body.…”
Background. Primary hypertension is a significant risk factor for cardiovascular diseases. However, the pathogenesis of primary hypertension involves multiple biological processes, including the nervous system, circulatory system, endocrine system, and more. Despite extensive research, there is no clear understanding of the regulatory mechanism underlying its pathogenesis. In recent years, miRNAs have gained attention as a regulatory factor capable of modulating the expression of related molecules through gene silencing. Therefore, exploring differentially expressed miRNAs in patients with essential hypertension (EH) may offer a novel approach for future diagnosis and treatment of EH. Methodology. This study included a total of twenty Han Chinese population samples from Hefei, China. The samples consisted of 10 healthy individuals and 10 patients with essential hypertension (EH). Statistical analysis was conducted to analyze the general information of the two sample groups. High-throughput sequencing and base identification were performed to obtain the original sequencing sequences. These sequences were then annotated using various databases including Rfam, cDNA sequences, species repetitive sequences library, and miRBase database. The number of miRNA species contained in the samples was measured. Next, TPM values were calculated to determine the expression level of each miRNA. The bioinformatics of the differentiated miRNAs were analyzed using the OECloud tool, and RPM values were calculated. Furthermore, the reliability of the expression was analyzed by calculating the area under the Roc curve using the OECloud tools. Results. Statistical analysis revealed no significant differences between the two samples in terms of age distribution, gender composition, smoking history, and alcohol consumption history (P > 0.05). However, there was a notable presence of family genetic history and high BMI in the EH population (P < 0.05). The sequencing results identified a total of 245 miRNAs, out of which 16 miRNAs exhibited differential expression. Among the highly expressed miRNAs were let-7d-5p, miR-101-3p, miR-122-5p, miR-122b-3p, miR-192-5p, and miR-6722-3p. On the other hand, the lowly expressed miRNAs included miR-103a-3p, miR-16-5p, miR-181a-2-3p, miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-221-3p, miR-30d-5p, miR-342-5p, and miR-543. Conclusion. This study initially identified 16 miRNAs that are aberrantly expressed and function in various processes associated with the onset and progression of essential hypertension. These miRNAs have the potential to be targeted for future diagnosis and treatment of EH. However, further samples are required to provide additional support for this study.
“…Once internalized through endocytosis by recipient cells, miRNAs play a crucial role in modulating cellular functions [3]. Generally, miRNAs regulate gene transcription, modulating key biological pathways, e.g., angiogenesis or cell migration [4].…”
Exosomes or small extracellular vesicles (sEVs) represent a pivotal component in intercellular communication, carrying a diverse array of biomolecules. Several factors can affect sEVs release dynamics, as occurs in hyperglycemia or inflammation. In fact, sEVs release has been associated with the promotion of physio-pathological processes. Among the sEVs cargo, microRNAs play an essential role in cell-to-cell regulation. More concretely, miR-205-5p is related to angiogenesis and cell proliferation. The aim of this study is to understand the specific role of sEVs containing miR-205-5p under high glucose conditions. ARPE-19 cells were cultured with high glucose (HG) for 5 days. sEVs were isolated and characterized. sEVs from ARPE-19 were used for angiogenesis and cell proliferation. HG increased sEVs release but downregulated miR-205-5p cargo expression compared to the control. sEVs from HG-treated ARPE-19 cells promoted tube formation and migration processes. In contrast, miR-205-5p overexpression (by mimic transfection) decreased angiogenesis and cell migration. Our results demonstrate how ARPE-19 cells respond to HG challenge by increasing sEVs with weak miR-205-5p cargo. The absence of this miRNA in sEVs is enough to promote angiogenesis. In contrast, restoring sEVs-miR-205-5p levels decreased it. These findings open new possibilities in sEVs-based therapies containing miR-205-5p against angiogenesis.
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