RESUMO
In the central nervous system (CNS), three types of myelin-associated inhibitors (MAIs) have major inhibitory effects on nerve regeneration. They include Nogo-A, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein. MAIs possess two co-receptors, Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Previous studies have confirmed that the inhibition of NgR only results in a modest increase in regeneration in the CNS; however, the inhibitory effects of PirB with regard to nerve regeneration after binding to MAIs remain controversial. In this study, we demonstrated that PirB is expressed in primary cultures of retinal ganglion cells (RGCs), and the inhibitory effects of the three MAIs on the growth of RGC neurites are not significantly decreased after direct PirB knockdown using adenovirus PirB shRNA. Interestingly, we found that retinal Müller cells expressed PirB and that its knockdown enhanced the regeneration of co-cultured RGC neurites. PirB knockdown also activated the JAK/Stat3 signaling pathway in Müller cells and upregulated ciliary neurotrophic factor levels. These findings indicate that PirB plays a novel role in retinal Müller cells and that its action in these cells may indirectly affect the growth of RGC neurites. The results also reveal that PirB in Müller cells affects RGC neurite regeneration. Our findings provide a novel basis for the use of PirB as a target molecule to promote nerve regeneration.
RESUMO
In the central nervous system (CNS), three types of myelin-associated inhibitors (MAIs) have major inhibitory effects on nerve regeneration. They include Nogo-A, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein. MAIs possess two co-receptors, Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Previous studies have confirmed that the inhibition of NgR only results in a modest increase in regeneration in the CNS; however, the inhibitory effects of PirB with regard to nerve regeneration after binding to MAIs remain controversial. In this study, we demonstrated that PirB is expressed in primary cultures of retinal ganglion cells (RGCs), and the inhibitory effects of the three MAIs on the growth of RGC neurites are not significantly decreased after direct PirB knockdown using adenovirus PirB shRNA. Interestingly, we found that retinal Müller cells expressed PirB and that its knockdown enhanced the regeneration of co-cultured RGC neurites. PirB knockdown also activated the JAK/Stat3 signaling pathway in Müller cells and upregulated ciliary neurotrophic factor levels. These findings indicate that PirB plays a novel role in retinal Müller cells and that its action in these cells may indirectly affect the growth of RGC neurites. The results also reveal that PirB in Müller cells affects RGC neurite regeneration. Our findings provide a novel basis for the use of PirB as a target molecule to promote nerve regeneration.
RESUMO
BACKGROUND: Transplantation of bone marrow mesenchymal stem cells (MSCs) improves functional recovery after spinal cord injury (SCl), but the mechanisms involved remain unclear.OBJECTIVE: To observe the effects of MSCs transplantation on the expression of brain-derived neurotrophic factors (BDNF) in rats after SCl.DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Laboratory of Neuroanatomy, China Medical University from April to July 2003.MATERIALS: A total of 64 SD rats, aged 3 months, of either gender, weighing 250-300 g, were used. Of them, 4 were randomly selected to isolate and culture MSCs, and the remaining were used to establish SCl models.METHODS: The 60 rats were randomly divided into 3 groups. Seven days after SCl, MSCs group (n=24) was transplanted with 5 μL culture solution containing 1×109/L MSCs to the injury site using micro-injection; PBS group (n=24) was transplanted with 5μ L PBS, and the blank control group (n=12) with 5μ L normal saline.MAIN OUTCOME MEASURES: The rats were sacrificed at 7, 14, and 28 days post-surgery. MSCs morphology was observed and the expression of BDNF at the lesion areas was examined by immunohistochemistry,RESULTS: All 60 rats were included in the final analysis. After ten subcultures, the cell proliferative capacity was reduced, and cell body turned to flat; the MSCs protiferation and morphous could be maintained by adding basic fibroblast growth factor.Transplantation of MSCs enhanced the expression of BDNF compared with PBS and blank control groups at 7, 14, and 28 days post-surgery (P ＜ 0.05); white no significant difference was found between PBS and blank control groups (P ＞ 0.05).