Effects of ADSC-Derived Exosome LRRC75A-AS1 on Anti-inflammatory Function After SCI.
Xiaohui XingPeng XuXiaoyang XingZhentao XuZhen HuangZhongchen LiXueyuan LiYilei XiaoPublished in: Applied biochemistry and biotechnology (2024)
Spinal cord injury (SCI) is a highly debilitating disorder of the central nervous system that can severely impact an affected patient's quality of life. This study aimed to examine how adipose-derived mesenchymal stem cell exosomes (ADSC-exos) can be used to treat spinal cord injury. We analysed differentially expressed mRNAs in SCI using bioinformatics data, gene expression profiles in inflammatory cell models, RT-qPCR and WB. Apoptosis was detected with flow cytometry. Starbase provides the control mechanism for FDFT1. Target interactions were detected with dual-luciferase reporter and RIP assays. Exosomes were isolated from adipose tissue-derived mesenchymal stem cells and subsequently characterized with western blot analysis, transmission electron microscopy and nanoparticle tracking analysis. By analysing the GSE102964 database, we found that FDFT1 was significantly downregulated as SCI progressed. Overexpression of FDFT1 can significantly reverse the inflammatory response and apoptosis of BV2 cells induced by hemin. Mechanically, ADSC-exos can affect the expression of FDFT1 through the ceRNA mechanism mediated by LRRC75A-AS1 and in an RBP-dependent manner mediated by IGF2BP2. The overexpression of LRRC75A-AS1 significantly enhances BV2 apoptosis and can be reversed by FDFT1 knockdown. ADSC-exos LRRC75A-AS1 inhibits inflammation and reduces SCI by increasing the expression and stability of FDFT1 mRNA in a ceRNA and RBP-dependent manner.
Keyphrases
- spinal cord injury
- cell cycle arrest
- oxidative stress
- mesenchymal stem cells
- inflammatory response
- spinal cord
- endoplasmic reticulum stress
- induced apoptosis
- cell death
- adipose tissue
- poor prognosis
- neuropathic pain
- flow cytometry
- pi k akt
- lipopolysaccharide induced
- long non coding rna
- lps induced
- binding protein
- cell proliferation
- electron microscopy
- stem cells
- anti inflammatory
- cell therapy
- transcription factor
- bone marrow
- insulin resistance
- umbilical cord
- single cell
- south africa
- type diabetes
- case report
- genome wide
- big data
- high fat diet
- immune response
- data analysis
- toll like receptor
- artificial intelligence