Wei Zhou1, Guandong Huang1, Jueming Ye1, Jiamei Jiang2, Qing Xu1. 1. Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People' Hospital, Shanghai, China. 2. Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People' Hospital, Shanghai, China, jingweizhang12@tom.com.
Abstract
OBJECTIVE: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease. Increasing evidence has documented the crucial role of microRNAs in ICH. The present study aimed to investigate the role and underlying mechanism of miR-340-5p in ICH. METHODS: The collagenase-induced ICH rat model was established. The neurological function of rats and the cerebral water content of rat brain tissue were measured to assess the brain injury. BV-2 cells were recruited and treated by LPS to mimic ICH-induced inflammatory response. qRT-PCR was used for the measurement of miR-340-5p. The protein levels of TNF-α, IL-6, and IL-1β were detected using ELISA. Luciferase reporter gene assay was performed to confirm the target gene. RESULTS: Downregulation of miR-340-5p was detected in the serum of ICH patients and the brain tissues of ICH rats. Overexpression of miR-340-5p reversed the influence of ICH on the neurological function score and cerebral water content and inhibited the production of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), which were induced by ICH in vivo. In in vitro study, levels of TNF-α, IL-6, and IL-1β were significantly enhanced in cells after LPS treatment, but these increases were eliminated by overexpression of miR-340-5p. PDCD4 was a direct target gene of miR-340-5p. CONCLUSION: miR-340-5p protects against brain injury after ICH. miR-340-5p might exert an anti-inflammatory effect during the occurrence of ICH via targeting PDCD4.
OBJECTIVE:Intracerebral hemorrhage (ICH) is a common cerebrovascular disease. Increasing evidence has documented the crucial role of microRNAs in ICH. The present study aimed to investigate the role and underlying mechanism of miR-340-5p in ICH. METHODS: The collagenase-induced ICHrat model was established. The neurological function of rats and the cerebral water content of rat brain tissue were measured to assess the brain injury. BV-2 cells were recruited and treated by LPS to mimic ICH-induced inflammatory response. qRT-PCR was used for the measurement of miR-340-5p. The protein levels of TNF-α, IL-6, and IL-1β were detected using ELISA. Luciferase reporter gene assay was performed to confirm the target gene. RESULTS: Downregulation of miR-340-5p was detected in the serum of ICHpatients and the brain tissues of ICHrats. Overexpression of miR-340-5p reversed the influence of ICH on the neurological function score and cerebral water content and inhibited the production of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), which were induced by ICH in vivo. In in vitro study, levels of TNF-α, IL-6, and IL-1β were significantly enhanced in cells after LPS treatment, but these increases were eliminated by overexpression of miR-340-5p. PDCD4 was a direct target gene of miR-340-5p. CONCLUSION:miR-340-5p protects against brain injury after ICH. miR-340-5p might exert an anti-inflammatory effect during the occurrence of ICH via targeting PDCD4.
Authors: Asha Rani; Jolie Barter; Ashok Kumar; Julie A Stortz; McKenzie Hollen; Dina Nacionales; Lyle L Moldawer; Philip A Efron; Thomas C Foster Journal: Aging (Albany NY) Date: 2022-01-30 Impact factor: 5.682
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