Spinal cord injury (SCI) is a state of severe neurological injury manifested as dysfunctions on the motion and nervous system, mainly resulting from the road traffic, sport, gun-shot accidents, infections, and vascular events [1,2]. SCI may cause lifetime disabilities including paraparesis, paraplegia, and quadriplegia, which can give rise to a heavy economic burden [3]. Though currently there are acute clinical methods, such as MAP augmentation, corticosteroid therapy, and early surgical decompression, SCI remains hard to be overcome due to its complex pathophysiology, considerable comorbidity, and patient heterogeneity [4]. As the largest number of glial cells existing in the central nervous system, astrocytes not only assume a role in homeostasis maintenance, synaptic plasticity development, and neuroprotection but also contribute to SCI progression under certain conditions [5]. Hence, molecular mechanisms underlying astrocyte functions need deep investigation to discover reliable therapeutic targets of SCI.

It has been implicated that microRNAs (miRs) participate in the pathogenesis of SCI [6]. miR-143, a miR encoded on chromosome 5, participates in the modulation of the cellular differentiation, apoptosis, and proliferation [7]. Strikingly, miR-143 was down-regulated in injured dorsal root ganglia during peripheral nerve injury triggered by the fifth spinal nerve ligation (SNL) [8]. As predicted by Starbase database in our study, there is a binding site between miR-143 and sirtuin 2 (SIRT2). The deacetylase SIRT2 resides in the cytoplasm, nucleus, and mitochondria and has numerous functions in the nervous system, genome integrity, and cell differentiation [9]. Furthermore, SIRT2 silencing augments the neurite outgrowth and length in organotypic spinal cord cultures and accelerates the functional motor recovery through following protections against peripheral nerve injury [10].

Histone acetylation is a dynamic process that regulates both inflammatory and anti-inflammatory genes, resulting in the activation or repression of genes through the regulation on histone acetyltransferases or deacetylases [11]. Histone acetylation was also defined as a regulator of gene expression [12]. SIRT2 has been reported to participate in protein deacetylation to modulate the expression of downstream genes [13]. Furthermore, the University of California Santa Cruz (UCSC) database used in the present research predicted the peak of H3 acetylation in the promoter of plasminogen activator urokinase receptor (PLAUR), indicating the potential association between SIRT2 and PLAUR. PLAUR, encompassing three domains and adhering to the cell membrane via a glycolipid anchor, exists in the plasminogen activation system and orchestrates cell-cell and cell-extracellular matrix interactions [14]. Interestingly, the deficiency of PLAUR functions in neurodegeneration after status epilepticus [15]. On this basis, a speculation was proposed that miR-143 might influence SCI via the SIRT2-PLAUR axis. Therefore, our research was designed to ascertain the mechanism of the miR-143-SIRT2-PLAUR axis in SCI with the focus on astrocyte functions.