Long noncoding RNA NKILA transferred by astrocyte-derived extracellular vesicles protects against neuronal injury by upregulating NLRX1 through binding to mir-195 in traumatic brain injury
Autor: | Ping Zheng, Wei Chen, Bin He, Wusong Tong, Jingsong Zeng |
---|---|
Rok vydání: | 2020 |
Předmět: |
Aging
microRNA-195 Traumatic brain injury Biology Cell Line Mitochondrial Proteins Extracellular Vesicles Mice Downregulation and upregulation In vivo long noncoding RNA NKILA Brain Injuries Traumatic medicine Animals Humans NLRX1 Neurons Cell growth traumatic brain injury Cell Biology medicine.disease Long non-coding RNA Cell biology Up-Regulation MicroRNAs medicine.anatomical_structure nervous system Gene Expression Regulation Apoptosis Astrocytes RNA Long Noncoding Astrocyte Research Paper |
Zdroj: | Aging (Albany NY) |
ISSN: | 1945-4589 |
Popis: | The study aims to investigate the effects of long noncoding RNA (lncRNA) transmitted nuclear factor-κB interacting lncRNA (NKILA)-containing astrocyte-derived small extracellular vesicles (EVs) on traumatic brain injury (TBI). TBI was modeled in vitro by exposing human neurons to mechanical injury and in vivo by controlled cortical impact in a mouse model. The gain- and loss-function approaches were conducted in injured neurons to explore the role of NKILA, microRNA-195 (miR-195) and nucleotide-binding leucine-rich repeat containing family member X1 (NLRX1) in neuronal injury. EVs extracted from NKILA-overexpressing astrocytes were used to treat injured neurons. It was revealed that NKILA was downregulated in injured neurons. Astrocyte co-culture participated in the upregulation of NKILA in injured neurons. Additionally, NKILA could competitively bind to miR-195 that directly targeted NLRX1. Next, the upregulation of NLRX1 or NKILA relived neuronal injury by promoting neuronal proliferation but inhibiting apoptosis. Astrocyte-derived EVs transferred NKILA into neurons, which led to the downregulation of miR-195, upregulation of NLRX1, increased cell proliferation, and decreased cell apoptosis. The in vivo experiments validated that NKILA-containing EVs promoted brain recovery following TBI. Collectively, astrocyte-derived EVs carrying NKILA was found to alleviate neuronal injury in TBI by competitively binding to miR-195 and upregulating NLRX1. |
Databáze: | OpenAIRE |
Externí odkaz: |