Salidroside mitigates hydrogen peroxide-induced injury by enhancement of microRNA-27a in human trabecular meshwork cells

Abstract

Salidroside (Sal) exerted widely pharmacological effects in multitudinous diseases had been certified. The actual study clarified the protective activity of Sal in H 2 O 2 -injured human trabecular meshwork (HTM) cells. HTM cells were disposed with H 2 O 2 to construct an oxidative damage model in vitro. Then, Sal was utilized to administrate HTM cells, and cell viability, apoptosis, apoptosis-interrelated proteins and ROS production were appraised using CCK-8, flow cytometry, western blot and DCFH-DA staining. MiR-27a inhibitor and its control were transfected into HTM cells, and the influences of miR-27a inhibition in HTM cells stimulated with H 2 O 2 and Sal were detected. PI3K/AKT and Wnt/b-catenin pathways were ultimately investigated to uncover the underlying mechanism. We found that H 2 O 2 evoked HTM cells oxidative damage, as evidenced by repressing cell viability, inducing apoptosis, activating cleavedcaspase-3/-9 expression and increasing ROS production. Sal significantly lightened H 2 O 2 -evoked oxidative damage in HTM cells. Additionally, miR-27a was up-regulated by Sal, and miR-27a suppression significantly reversed the protective effect of Sal on H 2 O 2 -injured HTM cells. Finally, Sal activated PI3K/ AKT and Wnt/b-catenin pathways through enhancement of miR-27a in H 2 O 2 -injured HTM cells. In conclusion, these discoveries suggested that Sal could protect HTM cells against H 2 O 2 -evoked oxidative damage by activating PI3K/AKT and Wnt/b-catenin pathways through enhancement of miR-27a. HIGHLIGHTS 1. H 2 O 2 evokes HTM cells oxidative damage; 2. Sal relieves H 2 O 2 -induced oxidative damage in HTM cells; 3. Sal enhances miR-27a expression in H 2 O 2 -injured HTM cells; 4. Repressed miR-27a reverses the protective impacts of Sal on H 2 O 2 -injured HTM cells; 5. Sal activates PI3K/AKT and Wnt/b-catenin pathways by increasing miR-27a.

Neuroinflammation in Primary Open-Angle Glaucoma

“…In addition, OIP5-AS1, which is an anti-sense lncRNA, was able to compete with several miRNAs, for example with hsa-miR-17-5p, hsa-miR-20b-5p, hsa-miR-761, hsa-miR-3619-5p, hsa-miR-24-3p, mir-27a and so on, and regulates the gene expressions [ 232 ]. Among these miRNAs, miR-27a, for instance, exerts a protective role on HTM cells under H 2 O 2 administration [ 246 ]. Another miRNA target of OIP5-AS1, which is also involved in glaucoma, is miR-17-5p.…”

The Potential Role of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in Glaucoma: A Review

“…The sources of trabecular meshwork oxidative stress include ultraviolet (UV)-based byproducts of the anterior chamber, excess ROS accumulation [33], and the imbalance between oxidants and antioxidants [6,34]. Studies have shown that in patients with POAG, the trabecular meshwork is exposed to ROS in aqueous humor, which suggests that ROS may have a causative role in glaucoma at the level of trabecular meshwork cells [35,36]. As one of the most sensitive ocular cells, the trabecular meshwork cell is a primary cell type that occupies and forms the proximal portion of the aqueous humor outflow pathway.…”

Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma

“…These miRNAs interacted with OIP5-AS1 and have been known to be involved in glaucoma. For example, Zhao's study has confirmed that miR-27a (a target miRNA of OIP5-AS1) has protective impacts on H2O2-injured human trabecular meshwork cells, which comprise a common glaucoma cell model [46]. Another miRNA (miR-17-5p, a target miRNA of OIP5-AS1) has been found to have the function of regulating the proliferation and apoptosis of human trabecular meshwork cells in response to oxidative stress [47].…”