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

Abstract

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.

Role of Purpurin as a Retinol-Binding Protein in Goldfish Retina during the Early Stage of Optic Nerve Regeneration: Its Priming Action on Neurite Outgrowth

“…The importance of retinoic acid and RALDH-2 is well known in developing retina (Mey et al, 1997;Stull and Wikler, 2000) and adult mouse dorsal root ganglia (Corcoran and Maden, 1999). Recently, the activation of retinoic acid signaling after sciatic nerve injury was reported in rats (Zhelyaznik et al, 2003).…”

“…Although we have tried to screen a rat homologous to purpurin cDNA, we cannot succeed it yet. Another retinol-binding protein might work in the other nervous system (Zhelyaznik et al, 2003).…”

Neuronal RARβ Signaling Modulates PTEN Activity Directly in Neurons and via Exosome Transfer in Astrocytes to Prevent Glial Scar Formation and Induce Spinal Cord Regeneration

“…Retinoic acid (RA) plays an essential role in the survival and differentiation of the vertebrate CNS and stimulates both neurite number and length in embryonic neuronal types (Maden, 2001). In the adult, RA-responsive elements are locally activated in the regenerating rat nerve after peripheral nerve injury (Zhelyaznik et al, 2003). In embryonic DRG neurons, RAR␤2 mediates neurite outgrowth induced by RA (Corcoran et al, 2000) and, in adult spinal cord explants, where RAR␤2 is absent, exogenous RAR␤2 stimulates neurite outgrowth (Corcoran et al, 2002).…”

Molecular mechanisms of reversing neural degeneration by retinoic acid, a major derivative of vitamin A

“…Probing into neurobiology and underlying signaling pathways regarding neural regeneration, stem cell proliferation and cell differentiation is one of the most promising area of research (Wuarin and Sidell, 1991;Wuarin et al, 1990;Zhelyaznik et al, 2003). However, complete molecular cross talking mechanisms remain ambiguous.…”