Role of Long Non-coding RNA in Nerve Regeneration.

Nerve injury can be caused by a variety of factors. It often takes a long time to repair a nerve injury and severe nerve injury is even difficult to heal. Therefore, increasing attention has focused on nerve injury and repair. Long non-coding RNA (lncRNA) is a newly discovered non-coding RNA with a wide range of biological activities. Numerous studies have shown that a variety of lncRNAs undergo changes in expression after nerve injury, indicating that lncRNAs may be involved in various biological processes of nerve repair and regeneration. Herein, we summarize the biological roles of lncRNAs in neurons, glial cells and other cells during nerve injury and regeneration, which will help lncRNAs to be better applied in nerve injury and regeneration in the future.

Claudin 14/15 play important roles in early wallerian degeneration after rat sciatic nerve injury.

PURPOSE: Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro. METHODS: Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD. RESULTS: It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the ß-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered. CONCLUSION: Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the ß-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.

Effect of Spp1 on nerve degeneration and regeneration after rat sciatic nerve injury.

BACKGROUND: Wallerian degeneration (WD) in injured peripheral nerves is associated with a large number of up- or down-regulated genes, but the effects of these changes are poorly understood. In our previous studies, we reported some key factors that are differentially expressed to activate nerve degeneration and regeneration during WD. Here, we determined the effects of secreted phosphoprotein 1 (Spp1) on WD after rat sciatic nerve injury. RESULTS: Spp1 was upregulated from 6 h to 14 days after sciatic nerve injury. Altered expression of Spp1 in Schwann cells (SC) resulted in altered mRNA and protein expression levels for cytokines, c-Fos, PKCα and phospho-ERK/ERK and affected SC apoptosis in vitro. Silencing of Spp1 expression in SCs using siRNA technology reduced proliferation and promoted migration of SCs in vitro. By contrast, overexpression of Spp1 promoted proliferation and reduced migration in SCs in vitro. Differential expression of Spp1 after sciatic nerve injury in vivo altered the expression of cytokines, c-Fos, PKCα, and the p-ERK/ERK pathway. CONCLUSIONS: Spp1 is a key regulatory factor that affects nerve degeneration and regeneration through c-Fos, PKCα and p-ERK/ERK pathways after rat sciatic nerve injury. These results shed new light on the role of Spp1 in nerve degeneration and regeneration during WD.

Abnormal expressions of inflammatory-related mediators and inhibition of fat metabolism in mice infected with influenza a virus.

The pathophysiological role of influenza infection is poorly understood. In this study, one non-neurovirulent virus (IAV/Aichi/2/68/H3N2) strain was used to infect intra-nasally mice at different age to investigate the mechanism of cerebral edema formation and lower activities of mitochondria enzymes after influenza A virus (IAV) infection. Mice suffered 46.4% mortality in newborn compared with 96.0% in weanling, 100% in adult on day 7, respectively. IAV-RNA was easily detected in the brain of newborn mice. Significant production of endothelin-1 and inducible nitric oxide syntheses were increased on the 3rd and 5th day after IAV infection, associated with increasing blood-brain barrier permeability, brain edema formation and the higher mortality of animals. Production of tumor necrosis factor-α was related to inhibition of mitochondrial enzyme activities, suggesting that over expression of inflammatory cytokines and lower enzyme activities in mitochondria after IAV infection.

Protein expression profiling during wallerian degeneration after rat sciatic nerve injury.

INTRODUCTION: Wallerian degeneration (WD) is an important area of research in modern neuroscience. Many protein expressions are regulated by differentially expressed genes in WD, but the precise mechanisms are elusive. METHODS: In this study, we profiled differentially expressed proteins in WD after rat sciatic nerve injury using an antibody array. RESULTS: Functional analysis positively identified cell proliferation, regulation of cell proliferation, and immune system processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed molecular networks related mainly to cytokine-cytokine receptor interaction, the mitogen-activated proteinkinase (MAPK) signaling pathway, apoptosis, the toll-like receptor (TLR) signaling pathway, and the Janus kinase (Jak) - signal transducer and activator of transcription (STAT) signaling pathway. Interactions between these differential proteins were well established and regulated by the key factors transforming growth factor beta 1 (TGF-ß1), toll-like receptor 4 (TLR4), Fas ligand (FasL), and 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1). CONCLUSIONS: These results provide information related to functional analysis of differentially expressed genes during WD.

Inflammation in the Peripheral Nervous System after Injury.

Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the degeneration of distal axons and myelin sheaths. Macrophages and Schwann cells (SCs) can phagocytose damaged cells. Wallerian degeneration (WD) makes the whole axon structure degenerate, creating a favorable regenerative environment for new axons. After nerve injury, macrophages, neutrophils and other cells are mobilized and recruited to the injury site to phagocytose necrotic cells and myelin debris. Pro-inflammatory and anti-inflammatory factors involved in the inflammatory response provide a favorable microenvironment for peripheral nerve regeneration and regulate the effects of inflammation on the body through relevant signaling pathways. Previously, inflammation was thought to be detrimental to the body, but further research has shown that appropriate inflammation promotes nerve regeneration, axon regeneration, and myelin formation. On the contrary, excessive inflammation can cause nerve tissue damage and pathological changes, and even lead to neurological diseases. Therefore, after nerve injury, various cells in the body interact with cytokines and chemokines to promote peripheral nerve repair and regeneration by inhibiting the negative effects of inflammation and harnessing the positive effects of inflammation in specific ways and at specific times. Understanding the interaction between neuroinflammation and nerve regeneration provides several therapeutic ideas to improve the inflammatory microenvironment and promote nerve regeneration.

Fas ligand regulate nerve injury and repair by affecting AKT, ß-catenin, and NF-κB pathways.

Objective: To investigate the regulatory effect of Fas-L on the repair and regeneration of peripheral extension injury in rats. Methods: This study aimed to explore the effects of Fas-L on apoptosis and axonal regeneration of dorsal root ganglion (DRG) cells in rat peripheral nerve repair and regeneration by using several relevant experimental techniques from the injured nerve animal model, cell biology, and molecular biology. Results: The expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Interference with Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis, while the overexpression of Fas-L is contrary to it. Moreover, Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in Sprague Dawley (SD) rats by affecting several signaling pathways, such as p-AKT/AKT, ß-catenin, and NF-κB. Conclusion: Fas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves. Significance statement: The expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis. Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in SD rats by affecting several signaling pathways, such as p-AKT/AKT, ß-catenin, and NF-κB. Fas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves.

Role of host cellular proteases in the pathogenesis of influenza and influenza-induced multiple organ failure.

Influenza A virus (IAV) is one of the most common infectious pathogens in humans. Since the IVA genome does not have the processing protease for the viral hemagglutinin (HA) envelope glycoprotein precursors, entry of this virus into cells and infectious organ tropism of IAV are primarily determined by host cellular trypsin-type HA processing proteases. Several secretion-type HA processing proteases for seasonal IAV in the airway, and ubiquitously expressed furin and pro-protein convertases for highly pathogenic avian influenza (HPAI) virus, have been reported. Recently, other HA-processing proteases for seasonal IAV and HPAI have been identified in the membrane fraction. These proteases proteolytically activate viral multiplication at the time of viral entry and budding. In addition to the role of host cellular proteases in IAV pathogenicity, IAV infection results in marked upregulation of cellular trypsins and matrix metalloproteinase-9 in various organs and cells, particularly endothelial cells, through induced pro-inflammatory cytokines. These host cellular factors interact with each other as the influenza virus-cytokine-protease cycle, which is the major mechanism that induces vascular hyperpermeability and multiorgan failure in severe influenza. This mini-review discusses the roles of cellular proteases in the pathogenesis of IAV and highlights the molecular mechanisms of upregulation of trypsins as effective targets for the control of IAV infection. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.

Long noncoding RNA H19 regulates degeneration and regeneration of injured peripheral nerves.

Our previous studies have shown that long noncoding RNA (lncRNA) H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration, and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons. However, the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear. In this study, we established a Sprague-Dawley rat model of sciatic nerve transection injury. We performed in situ hybridization and found that at 4-7 days after sciatic nerve injury, lncRNA H19 was highly expressed. At 14 days before injury, adeno-associated virus was intrathecally injected into the L4-L5 foramina to disrupt or overexpress lncRNA H19. After overexpression of lncRNA H19, the growth of newly formed axons from the sciatic nerve was inhibited, whereas myelination was enhanced. Then, we performed gait analysis and thermal pain analysis to evaluate rat behavior. We found that lncRNA H19 overexpression delayed the recovery of rat behavior function, whereas interfering with lncRNA H19 expression improved functional recovery. Finally, we examined the expression of lncRNA H19 downstream target SEMA6D, and found that after lncRNA H19 overexpression, the SEMA6D protein level was increased. These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves. This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.

Identification and functional analysis of novel micro-RNAs in rat dorsal root ganglia after sciatic nerve resection.

Peripheral nerve injures are quite common in clinical practice, and many studies have tried to explore the underlying molecular mechanisms. This study focuses on the identification and functional analysis of novel miRNAs in rat dorsal root ganglia (DRGs) following sciatic nerve resection, which is a classic model for studying peripheral nerve injury and regeneration. By using Solexa sequencing, computational analysis, Q-PCR verification, and Dicer knockdown assay, 114 novel miRNAs in rats were identified, of which 51 novel miRNAs were first reported in rat DRGs, and 63 novel miRNAs were produced at days 1, 4, 7, and 14 following sciatic nerve resection. We further predicted target genes of these miRNAs and analyzed the biological processes in which they were involved. The identified biological processes were consistent with the time frame of peripheral nerve injury and regeneration, revealing that these miRNAs were genuine miRNAs related to nerve regeneration. Our data provide an important resource for the future study of function and regulation of these miRNAs and contribute to elucidation of tyhe molecular mechanisms responsible for peripheral nerve injury and regeneration.

Baculoviral inhibitor of apoptosis protein repeat-containing protein 3 delays early Wallerian degeneration after sciatic nerve injury.

Wallerian degeneration is a complex biological process that occurs after nerve injury, and involves nerve degeneration and regeneration. Schwann cells play a crucial role in the cellular and molecular events of Wallerian degeneration of the peripheral nervous system. However, Wallerian degeneration regulating nerve injury and repair remains largely unknown, especially the early response. We have previously reported some key regulators of Wallerian degeneration after sciatic nerve injury. Baculoviral inhibitor of apoptosis protein repeat-containing protein 3 (BIRC3) is an important factor that regulates apoptosis-inhibiting protein. In this study, we established rat models of right sciatic nerve injury. In vitro Schwann cell models were also established and subjected to gene transfection to inhibit and overexpress BIRC3. The data indicated that BIRC3 expression was significantly up-regulated after sciatic nerve injury. Both BIRC3 upregulation and downregulation affected the migration, proliferation and apoptosis of Schwan cells and affected the expression of related factors through activating c-fos and ERK signal pathway. Inhibition of BIRC3 delayed early Wallerian degeneration through inhibiting the apoptosis of Schwann cells after sciatic nerve injury. These findings suggest that BIRC3 plays an important role in peripheral nerve injury repair and regeneration. The study was approved by the Institutional Animal Care and Use Committee of Nantong University, China (approval No. 2019-nsfc004) on March 1, 2019.

Effect of lncRNA H19 on nerve degeneration and regeneration after sciatic nerve injury in rats.

Hundreds of millions of people worldwide suffer from peripheral nerve damage resulting from car accidents, falls, industrial accidents, residential accidents, and wars. The purpose of our study was to further investigate the effects of Wallerian degeneration (WD) after rat sciatic nerve injury and to screen for critical long noncoding RNAs (lncRNAs) in WD. We found H19 to be essential for nerve degeneration and regeneration and to be highly expressed in the sciatic nerves of rats with WD. lncRNA H19 potentially impaired the recovery of sciatic nerve function in rats. H19 was mainly localized in the cytoplasm of Schwann cells (SCs) and promoted their migration. H19 promoted the apoptosis of dorsal root ganglion (DRG) neurons and slowed the growth of DRG axons. The lncRNA H19 may play a role in WD through the Wnt/ß-catenin signaling pathway and is coexpressed with a variety of crucial mRNAs during WD. These data provide further insight into the molecular mechanisms of WD.

Protein kinase C theta (Prkcq) affects nerve degeneration and regeneration through the c-fos and c-jun pathways in injured rat sciatic nerves.

BACKGROUND: Previous finding using DNA microarray and bioinformatics analysis, we have reported some key factors which regulated gene expression and signaling pathways in injured sciatic nerve during Wallerian Degeneration (WD). This research is focused on protein kinase C theta (Prkcq) participates in the regulation of the WD process. METHODS: In this study, we explored the molecular mechanism by which Prkcq in Schwann cells (SCs) affects nerve degeneration and regeneration in vivo and in vitro after rat sciatic nerve injury. RESULTS: Study of the cross-sectional model showed that Prkcq expression decreased significantly during sciatic nerve repair. Functional analysis showed that upregulation and downregulation of Prkcq could affect the proliferation, migration and apoptosis of Schwann cells and lead to the expression of related factors through the activation of the ß-catenin, c-fos, and p-c-jun/c-jun pathways. CONCLUSION: The study provides insights into the role of Prkcq in early WD during peripheral nerve degeneration and/or regeneration.

Suppression of human hepatoma (HepG2) cell growth by nuclear factor-kappaB/p65 specific siRNA.

Nuclear factor-kappaB (NF-κB) is a transcription factor and antagonist of apoptosis during liver regeneration and closely related to the formation and development of hepatocellular carcinoma. In the present study, we investigated the effect of small interference RNA (siRNA)-mediated inhibition of NF-κB on growth of human hepatoma (HepG2) cells. Our data indicated that the expression of NF-κB/p65 mRNA was significantly higher in the HepG2 cells than that in the normal liver (LO2) cells before transfection, and the expression of NF-κB/p65 in the HepG2 cells with NF-κB/p65 siRNA (100 nMol/L) transfection at 72 h was reduced at the levels of mRNA (93%) and protein (62%) using real-time reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. Interestingly, the apoptosis index of the HepG2 cells increased up to 85%, detected by Annexin V-fluorescein isothiocyanate, suggesting that NF-κB is overexpressed in hepatoma cells and can be inhibited by NF-κB/p65 siRNA through the apoptotic mechanism. Thus, we conclude that NF-κB is a potential molecular target for HCC gene therapy.

Claudin-15 overexpression inhibits proliferation and promotes apoptosis of Schwann cells in vitro.

Our previous experiments have discovered that Claudin-15 was up-regulated in Schwann cells of the distal nerve stumps of rat models of sciatic nerve injury. However, how Claudin-15 affects Schwann cell function is still unknown. This study aimed to identify the effects of Claudin-15 on proliferation and apoptosis of Schwann cells cultured in vitro and explore the underlying mechanisms. Primary Schwann cells were obtained from rats. Claudin-15 in Schwann cells was knocked down using siRNA (siRNA-1 group) compared with the negative control siRNA transfection group (negative control group). Claudin-15 in Schwann cells was overexpressed using pGV230-Claudin-15 plasmid (pGV230-Claudin-15 group). The pGV230 transfection group (pGV230 group) acted as the control of the pGV230-Claudin-15 group. Cell proliferation was analyzed with EdU assay. Cell apoptosis was analyzed with flow cytometric analysis. Cell migration was analyzed with Transwell inserts. The mRNA and protein expressions were analyzed with quantitative polymerase chain reaction assay and western blot assay. The results showed that compared with the negative control group, cell proliferation rate was up-regulated; p-AKT/AKT ratio, apoptotic rate, p-c-Jun/c-Jun ratio, mRNA expression of protein kinase C alpha, Bcl-2 and Bax were down-regulated; and mRNA expression of neurotrophins basic fibroblast growth factor and neurotrophin-3 were increased in the siRNA-1 group. No significant difference was found in cell migration between the negative control and siRNA-1 groups. Compared with the pGV230 group, the cell proliferation rate was down-regulated; apoptotic rate, p-c-Jun/c-Jun ratio and c-Fos protein expression increased; mRNA expression of protein kinase C alpha and Bax decreased; and mRNA expressions of neurotrophins basic fibroblast growth factor and neurotrophin-3 were up-regulated in the pGV230-Claudin-15 group. The above results demonstrated that overexpression of Claudin-15 inhibited Schwann cell proliferation and promoted Schwann cell apoptosis in vitro. Silencing of Claudin-15 had the reverse effect and provided neuroprotective effect. This study was approved by the Experimental Animal Ethics Committee of Jilin University of China (approval No. 2016-nsfc001) on March 5, 2016.

Protein Kinase Cα Promotes Proliferation and Migration of Schwann Cells by Activating ERK Signaling Pathway.

Wallerian degeneration (WD) and axon regeneration generally take place following peripheral nerve injury (PNI). Schwann cells (SCs) and macrophages play major role in WD. SCs, acting as repair cells and primary signal mediators, dedifferentiate and proliferate to remove the debris, form Büngner's bands and secrete trophic factors during these processes. However, the underlying mechanisms remain poorly understood. Here, we found that protein kinase Cα (PKCα), a serine/threonine kinase, expressed in SCs was significantly up-regulated after PNI. Activating PKCα with phorbol 12-myristate 13-acetate (PMA), a phorbol ester binds and activates PKCα) promoted SCs proliferation and migration. While, silence of PKCα by siRNAs inhibited these processes. PD184352, an inhibitor of MEK1, reversed the effect induced by PMA on SCs. Mechanism studies revealed that PKCα functioned through activating the ERK signaling pathway. Furthermore, PKCα also exhibited a neuroprotective role by upregulating the expression of neurotrophic factors in SCs. To sum up, this study offers novel insights for clarifying our understanding of the involvement of PKCα in the mechanism of peripheral nerve degeneration as well as regeneration.

Thermal instability of compound variants of carnitine palmitoyltransferase II and impaired mitochondrial fuel utilization in influenza-associated encephalopathy.

Influenza-associated encephalopathy (IAE) is characterized by persistent high fever, febrile convulsions, severe brain edema, and high mortality in otherwise apparently healthy individuals. We have reported that a large proportion of patients suffering from disabling or fatal IAE, with transiently elevated serum acylcarnitine during high fever, exhibit a thermolabile phenotype of compound homo-/heterozygous variants of carnitine palmitoyltransferase II (CPT II, gene symbol CPT2). We characterized the enzymatic properties of five single and three compound CPT II variants in patients with IAE. The kinetic characteristics of WT and variant CPT IIs, expressed in COS-7 cells, indicated that the variants exert a dominant-negative effect on the homotetrameric protein of the enzyme. Among the variants, three compound variations found in patients with severe encephalopathy; [c.1055T>G (p.Phe352Cys); c.1102G>A (p.Val368Ile)], [c.1511C>T (p.Pro504Leu); c.1813G>C (p.Val605Leu)], and [c.1055T>G (p.Phe352Cys); c.1102G>A (p.Val368Ile); c.1813G>C (p.Val605Leu)], showed reduced activities, thermal instability, and short half-lives compared with the WT. Like other disease-causing mutant proteins, these variant proteins were poly-ubiquitinated and rapidly degraded by a lactacystin-sensitive proteasome pathway. COS-7 cells transfected with the compound variants had their fatty acid beta-oxidation decreased to 30-59% and intracellular ATP levels to 48-79%, and a marked reduction of mitochondrial membrane potential at 41 degrees C, compared with control cells transfected with WT at 37 degrees C. The unstable CPT II variants with decreased enzymatic activities may bring mitochondrial fuel utilization below the phenotypic threshold during high fever, and thus may play an important etiopathological role in the development of brain edema of IAE.

Clinical impact of plasma TGF-beta1 and circulating TGF-beta1 mRNA in diagnosis of hepatocellular carcinoma.

BACKGROUND: Transforming growth factor-beta (TGF-beta) plays an important role in the regulation of cell growth and differentiation, angiogenesis, extracellular matrix formation, immunosuppression and cancer development. In this study, we investigated the levels of TGF-beta1 and TGF-beta1 mRNA expression, their relationship with HBV replication, and their diagnostic value for hepatocellular carcinoma (HCC). METHODS: Total RNAs were extracted from HCC samples and matched non-tumor tissues, and from peripheral blood mononuclear cells in HCC patients. TGF-beta1 mRNA was amplified by RT-PCR and confirmed by DNA sequencing. The distribution of TGF-beta1 expression was assessed by immunohistochemistry. The clinical characteristics were analyzed between TGF-beta1 and HBV replication. The diagnostic value of circulating TGF-beta1 and TGF-beta1 mRNA levels were investigated in HCC patients. RESULTS: The incidence of hepatic TGF-beta1 expression was 83.3% in HCC samples, 43.3% in the surrounding tissues, 94.7% in the HBV DNA-positive group, and 63.6% in the HBV DNA-negative group. Liver TGF-beta1 expression was associated with the degree of HCC differentiation and the status of HBV replication, but not with the size or number of tumors. Circulating TGF-beta1 level and incidence of TGF-beta1 mRNA were significantly higher in the HCC group than in any group of patients with benign liver disease, with a higher sensitivity of 89.5% and a specificity of 94.0% for HCC diagnosis when circulating TGF-beta1 levels were >1.2 microg/L. No significant correlation was found between TGF-beta1 expression and AFP level or tumor size. Combining TGF-beta1 level and serum AFP raised the detection rate to 97.4%. CONCLUSIONS: Abnormal expression of hepatic TGF-beta1 is associated with the degree of HCC differentiation and HBV replication. Both circulating TGF-beta1 and TGF-beta1 mRNA can be used as sensitive biomarkers for the diagnosis and prognosis of HBV-induced HCC.

Toll-Like Receptor 4 (TLR4) Expression Affects Schwann Cell Behavior in vitro.

Peripheral nerve injury can result in the decreased quality of life and bring us economic burden on society and individuals. Wallerian degeneration (WD) is critical for nerve degeneration and regeneration, but the mechanisms of WD are still elusive. Here, we report the effect of Toll-like receptor 4 (TLR4) on cultured Schwann cells (SCs) in vitro. The data showed that TLR4 expression was up-regulated after sciatic nerve injury of rat. TLR4 was expressed in cultured SCs. Enhanced or silenced expression of TLR4 affected SC proliferation, migration, apoptosis and relative gene expression. Furthermore, altered expression of TLR4 resulted in expression changes in c-Jun, ERK and catenin but not AKT and c-Fos pathways in SCs. These results suggested that TLR4 may be an important effective target in peripheral nerve degeneration and/or regeneration during WD in future investigations.

Fas Ligand Gene (Faslg) Plays an Important Role in Nerve Degeneration and Regeneration After Rat Sciatic Nerve Injury.

Wallerian degeneration (WD) is associated with changes in the expression levels of a large number of genes. However, the effects of these up- or down-regulated genes are poorly understood. We have reported some key factors that are differentially regulated during WD in our previous research. Here, we explored the roles of Fas ligand gene (Faslg) in WD after rat sciatic nerve injury. The data showed that Faslg was up-regulated in injured nerves. Expression changed of Faslg in Schwann cells (SCs) resulted in alterations in the release of related factors. Silencing or overexpression of Faslg affected SC proliferation, migration, and apoptosis through ß-catenin, nuclear factor-κB (NF-κB), and caspase-3 pathways in vivo and in vitro. Our data suggest that Faslg is a key regulatory gene that affects nerve repair and regeneration in peripheral nerve injury. This study sheds new light on the effects of Faslg on peripheral nerve degeneration and/or regeneration.