Molecular Mechanism of MiR-136-5p Targeting NF-κB/A20 in the IL-17-Mediated Inflammatory Response after Spinal Cord Injury

Abstract

Background/Aims: The pathophysiology of spinal cord injury (SCI) results in serious damage to the human body via an increase in the secondary biological processes imposed by activated astrocytes. Abnormal expression of microRNAs after SCI has become a potential research focus. However, the underlying mechanisms are poorly understood. Methods: SCI models were established in rats using Allen’s method, and the BBB scoring method was employed to assess locomotor function. Lentivirus was used to infect rat astrocytes and SCI rats. Real-time PCR and antibody chip were used to measure gene expression and cytokine secretion. Western blot analysis was employed to detect protein expression. HE staining was used to assess the histological changes in SCI. The immunohistochemical staining of A20 and p-NF-κB in SCI was also analyzed. Results: The in vitro experiment showed that miR-136-5p up-regulated the expression of p-NF-κB by down-regulating the expression of A20 so that astrocytes produced inflammatory factors and chemokines. The in vivo experiment indicated that overexpressed miR-136-5p promoted the production of inflammatory factors, chemokines and p-NF-κB in SCI rats, whereas it inhibited the expression of A20 protein and increased inflammatory cell infiltration and injuries in the spinal cord. Conclusion: The current findings indicate that silencing miR-136-5p effectively decreased inflammatory factors and chemokines and protected the spinal cord via NF-κB/A20 signaling in vivo and in vitro. In contrast, overexpression of miR-136-5p had the opposite effect.

Overexpression of microRNA-136-3p Alleviates Myocardial Injury in Coronary Artery Disease via the Rho A/ROCK Signaling Pathway

“…Moreover, the functional relevance of miR-136 in vascular endothelial cell apoptosis has been previously demonstrated, and the activities of vascular endothelial cells are clearly associated with cardiovascular diseases [15]. He et al [16] have found that miR-136-5p may act as a significant molecule for the modulation of spinal cord injury lesions in rat models and may be useful for treating this disease. Another study has suggested that expression of miR-136-3p was elevated at 6 h after human chorionic gonadotropin administration in rat ovaries and rat granulosa cells [17].…”

IL‐25 promotes cisplatin resistance of lung cancer cells by activating NF‐κB signaling pathway to increase of major vault protein

“…IL‐25 is an NF‐κB signaling pathway activator participating in multiple physiological processes of tumor cell, such as proliferation, apoptosis, and metastasis . Therefore, we supposed that IL‐25 mediates MVP expression by activating NF‐κB signaling pathway.…”

“…IL-25 is an NF-κB signaling pathway activator participating in multiple physiological processes of tumor cell, such as proliferation, apoptosis, and metastasis. 32,33 Therefore, we supposed that IL-25 mediates MVP expression by activating NF-κB signaling pathway. To confirm our hypothesis, we detected the expression of NF-κB signaling pathway-associated proteins by western blot in IL-25 overexpressed and silenced cells.…”

Triptolide improves spinal cord injury by promoting autophagy and inhibiting apoptosis

“…The recent increment in SCI cases could be attributed to a steady increase in vehicular accidents and falls (Chen et al, ). Traumatic SCI contributes to dyskinesia, chronic central pain, and subsequently intricate treatment (He et al, ). Secondary SCI, such as autophagy and apoptosis, could damage neighboring neurons that are not destroyed during the primary SCI, dramatically impacting the motor function recovery process (Tang et al, ).…”