BAMBI inhibits inflammation through the activation of autophagy in experimental spinal cord injury

Int J Mol Med. 2017 Feb;39(2):423-429. doi: 10.3892/ijmm.2016.2838. Epub 2016 Dec 27.

Abstract

Autophagy plays an important role in the progression of spinal cord injury (SCI). In this study, we aimed to examine the effects and potential mechanisms of action of BMP and activin membrane-bound inhibitor (BAMBI) in the progression of SCI. A rat model of SCI was established and the rats were injected with pLentiH1-BAMBI shRNA and pAd-BAMBI in the gray and white matter of the spinal cord at T8. After 14 days, motor function evaluation was measured according to the Basso Beattie Bresnahan (BBB) method and the number of motor neuron cell accounts in the anterior horns was measured by Nissl staining. The protein expression of levels light chain 3B (LC3B), Beclin 1, Bim and p62 were measured by western blot analysis. The concentrations of interleukin (IL)-1β, IL-6 and IL-10 were measured by ELISA. The results revealed that BAMBI expression was significantly decreased in the rats with SCI. The BBB scores and the number of motor neuron cell accounts in the anterior horns were significantly decreased in the pLentiH1-BAMBI shRNA injection group, and were increased in the pAd-BAMBI injection group, suggesting a neuroprotective effect of BAMBI in SCI. Moreover, the increased expression levels of LC3B and Beclin 1, and the decreased expression of Bim and p62 indicated that autophagy was significantly induced in the pAd-BAMBI injection group. Moreover, the overexpression of BAMBI also decreased the expression of transforming growth factor-β (TGF-β) and mammalian target of rapamycin (mTOR), and decreased the concentrations of IL-1β, IL-6 and IL-10. These results indicate that BAMBI plays a neuroprotective role by decreasing inflammation and activating autophagy in rats with SCI.

MeSH terms

  • Animals
  • Autophagy*
  • Disease Models, Animal
  • Gene Expression
  • Gene Knockdown Techniques
  • Gene Silencing
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Locomotion / genetics
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Rats
  • Signal Transduction
  • Spinal Cord Injuries / etiology*
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Bambi protein, rat
  • Membrane Proteins
  • RNA, Small Interfering
  • TOR Serine-Threonine Kinases