FOXG1 interaction with SATB2 promotes autophagy to alleviate neuroinflammation and mechanical abnormal pain in rats with lumbar disc herniation

Most patients with lumbar disc herniation can be relieved or cured by surgical or non-surgical treatment; however, postoperative persistent radiculopathy is common. This study demonstrates the regulation of autophagy by the FOXG1/SATB2 axis in lumbar disc herniation (LDH).

MiR-31a-5p/SATB2 is involved in the treatment of L. paracasei S16 in LDH rats. Overexpression of FOXG1 promotes autophagy through SATB2 to improve LDH levels This provides a new approach for the treatment of LDH.

Rat dorsal root neurons were induced with TNF-α in vitro. Sprague Dawley (SD) rats were used to construct the LDH rat model, which was treated with L. paracasei S16 or oe-FOXG1. Paw withdrawal threshold or latency assay (PWT/L) was performed. Peripheral blood samples were collected and analysed using ELISA and miRNAseq. RT-qPCR was used to analyse the expression of FOXG1, LC3B, Beclin1, p62, and SATB2. TUNEL staining and flow cytometry were used to analyse apoptosis. The expression of Cyclin D1, PCNA, Ki67, FOXG1, SATB2, and autophagy proteins was measured using western blotting.

TNF-α induced low expression of FOXG1 and SATB2 in dorsal root ganglion (DRG) neurons of rats. TNF-α induced an increase in p62 protein and a decrease in LC3II/I and Beclin-1 proteins in neurons, which were blocked by oe-FOXG1. oe-FOXG1 suppressed inflammation and apoptosis in TNF-α-induced DRG neurons and LDH rats and promoted the expression of Cyclin D1, PCNA, and Ki67. Many miRNAs were increased in the peripheral blood of LDH rats, but decreased after L. paracasei S16 intervention. L. paracasei S16 affects miR-31a-5p and SATB2 expression. Dual luciferase reporter gene assay confirmed that miR-31a-5p bound to SATB2. Co-IP analysis confirmed the interaction between FOXG1 and SATB2. Silencing of SATB2 inhibited the beneficial effects of oe-FOXG1 in TNF-α-induced dorsal root ganglion neurons. Animal experiments further demonstrated that oe-FOXG1 improved LDH disease characteristics by downregulating PWT, PWL, inflammation, and apoptosis levels and upregulating SATB2-autophagy levels. Conclusions: MiR-31a-5p/SATB2 is involved in the treatment of L. paracasei S16 in LDH rats. Overexpression of FOXG1 promotes autophagy through SATB2 to improve LDH levels This provides a new approach for the treatment of LDH.