Ning Dong1, Bing Xu2, Hong Shi2. 1. Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China. eye_dongning@163.com. 2. Department of Ophthalmology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.
Abstract
OBJECTIVE: To determine whether the long noncoding RNA MALAT1 may be involved in the inflammatory effect of Amadori-glycated albumin (AGA) in retinal microglia via a microRNA-124 (miR-124)-dependent mechanism. METHODS: Diabetes mellitus was induced by streptozotocin (STZ) injection. The expression of monocyte chemotactic protein-1 (MCP-1) in the retinas of rats was determined using quantitative reverse transcription-PCR (qRT-PCR) analyses and enzyme-linked immunosorbent assay (ELISA). Both qRT-PCR and ELISA were used to detect the levels of MCP-1 mRNA and soluble MCP-1 protein in the primary rat retinal microglia treated with AGA. The regulation of a putative target of miR-124 was validated by luciferase reporter assays. RESULTS: MALAT1 knockdown ameliorated diabetic retinopathy (DR) and inhibited MCP-1 release in the retinas of STZ-induced diabetic rats. The cultured retinal microglial cells treated with AGA-released MCP-1 in a dose- and time-dependent manner. In addition, AGA consistently induced MALAT1 expression in the retinal microglial cells. Next, we demonstrated that the expression of MCP-1 is controlled by miR-124, which binds to the 3'-UTR of MCP-1 in microglial cells. Luciferase reporter assays and RNA-binding protein immunoprecipitation assays showed that MALAT1 targets miR-124. Finally, we demonstrated that MALAT1 acts as a competing endogenous RNA by directly binding to miR-124 to regulate AGA-induced MCP-1 expression in microglial cells. CONCLUSIONS: MALAT1-miR-124-MCP-1 signaling pathway may be involved in AGA-induced MCP-1 expression in microglial cells, which may provide a new approach for the treatment of DR.
OBJECTIVE: To determine whether the long noncoding RNA MALAT1 may be involved in the inflammatory effect of Amadori-glycated albumin (AGA) in retinal microglia via a microRNA-124 (miR-124)-dependent mechanism. METHODS:Diabetes mellitus was induced by streptozotocin (STZ) injection. The expression of monocyte chemotactic protein-1 (MCP-1) in the retinas of rats was determined using quantitative reverse transcription-PCR (qRT-PCR) analyses and enzyme-linked immunosorbent assay (ELISA). Both qRT-PCR and ELISA were used to detect the levels of MCP-1 mRNA and soluble MCP-1 protein in the primary rat retinal microglia treated with AGA. The regulation of a putative target of miR-124 was validated by luciferase reporter assays. RESULTS:MALAT1 knockdown ameliorated diabetic retinopathy (DR) and inhibited MCP-1 release in the retinas of STZ-induced diabeticrats. The cultured retinal microglial cells treated with AGA-released MCP-1 in a dose- and time-dependent manner. In addition, AGA consistently induced MALAT1 expression in the retinal microglial cells. Next, we demonstrated that the expression of MCP-1 is controlled by miR-124, which binds to the 3'-UTR of MCP-1 in microglial cells. Luciferase reporter assays and RNA-binding protein immunoprecipitation assays showed that MALAT1 targets miR-124. Finally, we demonstrated that MALAT1 acts as a competing endogenous RNA by directly binding to miR-124 to regulate AGA-induced MCP-1 expression in microglial cells. CONCLUSIONS:MALAT1-miR-124-MCP-1 signaling pathway may be involved in AGA-induced MCP-1 expression in microglial cells, which may provide a new approach for the treatment of DR.
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