MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6.
I-Ting LinYu-Han LinWei-Shiung LianFeng-Sheng WangRe-Wen WuPublished in: International journal of molecular sciences (2023)
Spinal epidural fibrosis is one of the typical features attributable to failed back surgery syndrome, with excessive scar development in the dura and nerve roots. The microRNA-29 family (miR-29s) has been found to act as a fibrogenesis-inhibitory factor that reduces fibrotic matrix overproduction in various tissues. However, the mechanistic basis of miRNA-29a underlying the overabundant fibrotic matrix synthesis in spinal epidural scars post-laminectomy remained elusive. This study revealed that miR-29a attenuated lumbar laminectomy-induced fibrogenic activity, and epidural fibrotic matrix formation was significantly lessened in the transgenic mice (miR-29aTg) as compared with wild-type mice (WT). Moreover, miR-29aTg limits laminectomy-induced damage and has also been demonstrated to detect walking patterns, footprint distribution, and moving activity. Immunohistochemistry staining of epidural tissue showed that miR-29aTg was a remarkably weak signal of IL-6, TGF-β1, and DNA methyltransferase marker, Dnmt3b, compared to the wild-type mice. Taken together, these results have further strengthened the evidence that miR-29a epigenetic regulation reduces fibrotic matrix formation and spinal epidural fibrotic activity in surgery scars to preserve the integrity of the spinal cord core. This study elucidates and highlights the molecular mechanisms that reduce the incidence of spinal epidural fibrosis, eliminating the risk of gait abnormalities and pain associated with laminectomy.
Keyphrases
- spinal cord
- cell proliferation
- long non coding rna
- neuropathic pain
- wild type
- spinal cord injury
- long noncoding rna
- minimally invasive
- systemic sclerosis
- idiopathic pulmonary fibrosis
- high glucose
- transforming growth factor
- chronic pain
- oxidative stress
- dna methylation
- risk factors
- circulating tumor cells
- adipose tissue
- single molecule
- metabolic syndrome
- circulating tumor
- coronary artery bypass
- epithelial mesenchymal transition
- single cell
- radiation therapy
- physical activity
- wound healing
- skeletal muscle