Dynamic pattern of reg-2 expression in rat sensory neurons after peripheral nerve injury.
The 16 kDa pancreatitis-associated protein Reg-2 has recently been shown to facilitate the regeneration of motor and sensory neurons after peripheral nerve injury in the adult rat. Reg-2 has also been shown to be a neurotrophic factor that is an essential intermediate in the pathways through which CNTF supports the survival of motor neurons during development. Here we report the dynamic expression of Reg-2 in rat sensory neurons after peripheral nerve injury. Reg-2 is normally not expressed by dorsal root ganglion (DRG) cells, but we show, using immunocytochemistry, that Reg-2 is rapidly upregulated in DRG cells after sciatic nerve transection and after 24 hr recovery is expressed almost exclusively in small-diameter neurons that bind the lectin Griffonia simplicifolia IB4 and express the purinoceptor P2X3. However, by 7 d after axotomy, Reg-2 is expressed in medium to large neurons and coexists partly with the neuropeptides galanin and neuropeptide Y, which are also upregulated after peripheral nerve transection. At this time point, Reg-2 is no longer expressed in small neurons, and there is no colocalization with IB4 binding neurons, demonstrating a shift in Reg-2 expression from one subset of DRG neurons to another. We also show by double labeling for activating transcription factor 3, a transcription factor that is upregulated after nerve injury, that Reg-2 expression occurs predominantly in axotomized DRG cells but that a small percentage of uninjured DRG cells also upregulate Reg-2. The selective expression within IB4/P2X3 cells, and the dynamic shift from small to large cells, is unique among DRG peptides and suggests that Reg-2 has a distinctive role in the injury response.
Department of Neuroscience, Queen Mary University of London, London, E1 4NS, United Kingdom.
Sharon
S
Averill
Danny R
DR
Davis
Peter J
PJ
Shortland
John V
JV
Priestley
Stephen P
SP
Hunt
D051700:Activating Transcription Factor 3; D000818:Animals; D001370:Axonal Transport; D019771:Axotomy; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D048429:Cell Size; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D051847:Lithostathine; D008161:Lumbosacral Region; D008297:Male; D009409:Nerve Crush; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology; D000073718:Pancreatitis-Associated Proteins; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000503:physiopathology*; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D002135:Calcium-Binding Proteins; D051847:Lithostathine; D009419:Nerve Tissue Proteins; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C497616:Reg1a protein, rat; D014157:Transcription Factors