microRNA-143 targets SIRT2 to mediate the histone acetylation of PLAUR and modulates functions of astrocytes in spinal cord injury

• Published in: Chemico-biological interactions Vol. 390; p. 110854
• Main Authors: Wang, Changsheng, Zhu, Yi, Chen, Rongsheng, Zhu, Xitian, Zhang, Xiaobo
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 25.02.2024
• Subjects: Acetylation; Animals; Astrocytes; Histone acetylation; Histones - metabolism; Hyperplasia - metabolism; microRNA-143; MicroRNAs - metabolism; PLAUR; Rats; SIRT2; Sirtuin 2 - genetics; Sirtuin 2 - metabolism; Spinal Cord - metabolism; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal cord injury; Transforming Growth Factor beta - metabolism; Vimentin - genetics; Vimentin - metabolism; PLAUR; microRNA-143; Histone acetylation; Spinal cord injury; Astrocytes; SIRT2
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2023.110854

This study aimed to explore effects of microRNA (miR)-143 on the proliferation, apoptosis, and cytokine secretion in astrocytes after spinal cord injury (SCI). After gain- and loss-of-function assays and transforming growth factor (TGF)-β stimulation in astrocytes, the cell viability, proliferation, and apoptosis were examined. The expression of miR-143, SIRT2, and PLAUR and levels of astrocyte-related glial fibrillary acidic protein (GFAP), Vimentin, chondroitin sulfate proteoglycan (CSPG), and connective tissue growth factor (CTGF) were also measured. The binding relationship between miR-143 and SIRT2 was assessed, as well as the correlation of PLAUR with SIRT2. In established SCI rat models, the locomotion function and astrocyte hyperplasia were detected. The TGF-β stimulation decreased miR-143 but increased SIRT2 expression in astrocytes. Mechanistically, miR-143 negatively targeted SIRT2 and SIRT2 down-regulation inhibited the H3K27 deacetylation of PLAUR promoter to increase PLAUR expression. miR-143 up-regulation inhibited TGF-β stimulated-proliferation, promoted cell apoptosis, and reduced GFAP, Vimentin, CSPG, and CTGF expression in astrocytes, which was counterweighed by SIRT2 overexpression. SIRT2 silencing reduced the proliferation and GFAP, Vimentin, CSPG, and CTGF expression while augmenting the apoptosis in TGF-β stimulated astrocytes, which was abrogated by PLAUR silencing. The injection of miR-143 agomir improved the locomotion function and reduced the astrocyte hyperplasia in SCI rats, which was reversed by silencing PLAUR. miR-143 targeted SIRT2 to affect PLAUR expression via the regulation of histone acetylation, which repressed the astrocyte activation in vivo and in vitro to improve the locomotion function in SCI rats. •miR-143 suppresses AST hyperplasia and cytokine expression.•miR-143 modulates TGF-β-induced AST functions via SIRT2.•Down-regulation of SIRT2 inhibits H3K27 deacetylation of PLAUR promoter.•PLAUR silencing reverses effects of SIRT2 silencing on TGF-β-induced AST functions.•miR-143 improves locomotion function and AST cytokine expression in SCI rats.