Trim47 is a critical regulator of cerebral ischemia-reperfusion injury through regulating apoptosis and inflammation

Biochem Biophys Res Commun. 2019 Aug 6;515(4):651-657. doi: 10.1016/j.bbrc.2019.05.065. Epub 2019 Jun 6.


Cerebral ischemia is a leading cause of death and long-term disability in the world. Tripartite motif-47 (Trim47), a member of the TRIM family proteins, has been reported to be involved in apoptosis and inflammation in various types of diseases. Nevertheless, the underlying molecular mechanism of Trim47 in cerebral ischemia/reperfusion (I/R) injury remains unclear. This study aimed to explore the role of Trim47 in cerebral I/R injury and the potential underlying mechanisms. The results indicated that Trim47 expression was markedly induced in rats after stroke onset. By the use of genetic approaches, we indicated that Trim47 knockdown significantly reduced the infarct size, mitigated the neurological deficits scores and decreased brain water contents in rats with cerebral I/R injury induced by middle cerebral artery occlusion (MCAO). In addition, Trim47 knockdown-alleviated cerebral I/R was correlated with the suppression of apoptosis through inhibiting Caspase-3 cleavage. Furthermore, reducing Trim47 apparently decreased the release of pro-inflammatory factors, including interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), in brain samples of MCAO rats, which was partly by the blockage of nuclear factor-kappa B (NF-κB) signaling. However, Trim47 over-expression markedly accelerated cerebral ischemia injury through promoting apoptosis and inflammation. The suppressive effects of Trim47 knockdown on cerebral I/R were verified in human neuron-like cells stimulated by oxygen and glucose deprivation (OGD). Thus, this study demonstrated a new mechanism for the effect of Trim47 on cerebral I/R injury, and targeting Trim47 might provide feasible therapies for stroke treatment.

Keywords: Apoptosis; Cerebral ischemia; Inflammation; Trim47.

MeSH terms

  • Animals
  • Apoptosis*
  • Brain Ischemia / pathology*
  • Carrier Proteins / metabolism*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Humans
  • Infarction, Middle Cerebral Artery
  • Inflammation / metabolism*
  • Interleukin-6 / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / pathology*
  • Signal Transduction
  • Stroke / pathology*
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / physiology*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / physiology*


  • Carrier Proteins
  • Il6 protein, rat
  • Interleukin-6
  • Tripartite Motif Proteins
  • Trim47 protein, rat
  • Ubiquitin-Protein Ligases
  • Casp3 protein, rat
  • Caspase 3