Abstract
We have previously found that connexin43 is phosphorylated by extracellular-signal-regulated kinase (ERK)1/2 in rats of cerebral ischemia. Here, we investigated the potential roles of microRNA (miR)-302 cluster in the regulation of ERK1/2 mediated connexin43 phosphorylation and protection from traumatic brain injury (TBI) induced brain damage. We examined apoptosis and ERK1/2 and connexin43 phosphorylation in SH-SY5Y cells undergoing pulsatile shear stress treatment. We assessed expression of miR-302 cluster members and exogenously expressed miR-302 cluster in stressed cells to determine its effect on ERK1/2 and connexin43 phosphorylation. Finally, we investigated the effects of elevated miR-302 expression on cognitive function and brain damage in TBI rats generated by the controlled cortical impact method. Pulsatile shear stress leads to increased apoptosis and upregulation of ERK1/2 and connexin43 phosphorylation in vitro. Additionally, pulsatile shear stress significantly suppressed miR-302 expression and exogenously expression of miR-302 cluster inhibited ERK1/2 and connexin43 phosphorylation. Finally, elevated expression of miR-302 cluster not only improved cognitive function of TBI rats but also attenuated brain damage by suppressing edema and reducing contusion volume. Our study suggests that miR-302 protects rats from TBI induced brain damage and cognitive impairment and may represent an effective therapeutic strategy for TBI.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.