Ripasudil alleviated the inflammation of RPE cells by targeting the miR-136-5p/ROCK/NLRP3 pathway

Abstract

Background Inflammation of RPE cells led to different kinds of eye diseases and affected the normal function of the retina. Furthermore, higher levels of ROCK1 and ROCK2 induced injury of endothelial cells and many inflammatory diseases of the eyes. Ripasudil, which was used for the treatment of glaucoma, was one kind of the inhibitor of ROCK1 and ROCK2, but whether ripasudil could relieve the LPS-induced inflammation and damage of RPE cells was not clear. Methods We used LPS to stimulate ARPE-19 cells, the RPE cell line. After that, we detected the levels of ROCK1 and ROCK2 by western-blotting after the stimulation of LPS and treatment of ripasudil. Then luciferase reporter assays were used to confirm the targeting effect of miR-136-5p on ROCK1 and ROCK2. At last, the levels of NLRP3, ASC, caspase1, IL-1β and IL-18 were detected with the western-blotting after the knockdown of miR-136-5p. Results The levels of ROCK1, ROCK2 and miR-136-5p in ARPE-19 cells were promoted after the stimulation of LPS. After the treatment of ripasudil, the expression levels of ROCK1, ROCK2 and miR-136-5p were suppressed. The expression of ROCK1 and ROCK2 was targeted and inhibited by the miR-136-5p. The levels of inflammation related proteins NLRP3, ASC, caspase1, IL-1β and IL-18 was also inhibited after the treatment of ripasudil. However, the expression of these proteins was rescued after the knockdown of miR-136-5p. Conclusion Ripasudil relieved the inflammatory injury of RPE cells by upregulating miR-136-5p, therefore inhibiting the expression of ROCK1, ROCK2, NLRP3, ASC, caspase1, IL-1β and IL-18.

Circ_0001818 Targets Mir-136-5p to Increase Lipopolysaccharide-Induced Hk2 Cell Injuries by Activating Txnip/Nlrp3 Inflammasome Pathway

“…MiR-136-5p was shown to be involved in retinopathy, evidenced by its aberrant downregulation of miR-136-5p in LPS-treated retinal pigment epithelium cells (27). MiR-136-5p repression enhanced the production of inflammatory factors in LPS-treated retinal pigment epithelium cells (27). Besides, miR-136-5p was also involved in AKI, evidenced by its poor expression in HK2 cells treated with hypoxia/reoxygenation (28).…”

Differential Spleen miRNA Expression Profile of Beagle Dogs Infected with Toxocara canis

“…At 36 dpi, cfa-miR-136 was downregulated 1.91 times. The upregulation of cfa-miR-136 alleviates inflammatory injury [ 52 ]. IL17f , one of the potential target genes of cfa-miR-136, was successfully assigned to 15 significantly enriched GO terms at 36 dpi, such as regulation of inflammatory response, regulation of response to stimulus, and regulation of response to wounding.…”

Grape Seed Proanthocyanidins (GSPs) Inhibit the Development of Cutaneous Squamous Cell Carcinoma by Regulating the hsa_circ_0070934/miR-136-5p/PRAF2 Axis

“… 25 In addition, miR-136-5p also could suppress chondrocyte degeneration 26 and was related to the inflammation of retinal pigment epithelial. 27 Sand et al analyzed the differentially expressed miRNA in CSCC and normal skin tissue, and found that miR-136 was a significantly downregulated miRNA in CSCC. 28 In this study, our data suggested that miR-136-5p could be promoted by GSPs in vitro and in vivo, and it also could reverse the enhancing effect of hsa_circ_0070934 on the progression of GSPs-treated CSCC cells.…”