Background: Traumatic brain injury (TBI) has ranked as one of the leading causes of disability and death in the world. The neuroinflammation mediated by signal transducer and activator of transcription 3 (STAT3) signaling during the progression of TBI leads to long-term neurodegeneration. Ring finger protein 6 (RNF-6) is an E3 ubiquitin ligase and can regulate the activity of STAT3 signaling pathway by targeting its inhibitors. However, the mechanism underlying this process in TBI remains poorly understood.
Methods: In this research, cortical impact injury was used to construct the TBI rat model. Western blot assay was performed to evaluate the protein levels of RNF6, Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), and STAT3/pSTAT3. QRT-PCR assay was performed to assess the RNA levels of RNF6 and other cytokines. The neural function of TBI rats was estimated by modified Neurological Severity Scores test.
Results: The expression of RNF-6 was up-regulated in the brain tissues of TBI rats. Down-regulation of RNF6 alleviated the symptoms and improved the neural recovery postinjury in TBI rats. Inhibition of RNF6 suppressed the cerebral inflammation by up-regulating the protein level of SHP-1 and down-regulating the phosphorylation level of STAT3.
Conclusion: Inhibition of RNF6 alleviated TBI by suppressing the STAT3 signaling in TBI rats.
Keywords: JAK-STAT3 signaling pathway; SH2-containing tyrosine phosphatase-1 (SHP-1); ring finger protein 6; traumatic brain injury.
© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.