Activation of retinoic acid signalling after sciatic nerve injury: up-regulation of cellular retinoid binding proteins

Nina Zhelyaznik, Kirsten Schrage, Peter McCaffery, Jörg Mey

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54 Citations (Scopus)


In mammalian peripheral nerves a crush lesion causes interactions between injured neurons, Schwann cells and haematogenous macrophages that can lead to successful axonal regeneration. We suggest that the transcriptional activator retinoic acid (RA), takes part in gene regulation after peripheral nerve injury and that RA signalling is activated via the cellular retinoic acid binding protein (CRABP)-II and cellular retinol binding protein (CRBP)-I. With RT-PCR and immunoblotting all necessary components of the RA signalling pathway were detected in the sciatic nerve of adult rats. These are retinoic acid receptors, retinoid X receptors, the retinoic acid synthesizing enzymes RALDH-1, RALDH-2, and RALDH-3, in addition, the cellular retinoid binding proteins CRBP-I, CRABP-I and CRABP-II. Enzyme activity of RALDH-2 was detectable in the nerve, and using a transgenic reporter mouse we found local activation of RA responsive elements in the regenerating nerve. Sciatic nerve crush as well as transection resulted in a more than 10-fold up-regulation of CRBP-I, which is thought to facilitate the synthesis of RA. Both kinds of injury also caused a 15-fold increase in transcript and protein concentration of CRABP-II, a possible mediator of RA transfer to its nuclear receptors.
Original languageEnglish
Pages (from-to)1033-1040
Number of pages8
JournalEuropean Journal of Neuroscience
Issue number5
Publication statusPublished - 2003


  • Aldehyde Oxidoreductases
  • Animals
  • Blotting, Western
  • Colorimetry
  • Cytochrome P-450 Enzyme System
  • Gene Expression Regulation
  • Immunohistochemistry
  • Keratolytic Agents
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Crush
  • Neurofilament Proteins
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Retinoic Acid
  • Retina
  • Retinal Dehydrogenase
  • Retinoid X Receptors
  • Retinol-Binding Proteins
  • Retinol-Binding Proteins, Cellular
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Proteins
  • Sciatic Nerve
  • Signal Transduction
  • Time Factors
  • Transcription Factors
  • Tretinoin
  • Up-Regulation


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