Yan Liu

Nantong University, Tungchow, Jiangsu, China

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Publications (56)143.85 Total impact

  • No preview · Article · Feb 2016 · Scientific Reports
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    ABSTRACT: Reptiles are the most morphologically and physiologically diverse tetrapods, and have undergone 300 million years of adaptive evolution. Within the reptilian tetrapods, geckos possess several interesting features, including the ability to regenerate autotomized tails and to climb on smooth surfaces. Here we sequence the genome of Gekko japonicus (Schlegel's Japanese Gecko) and investigate genetic elements related to its physiology. We obtain a draft G. japonicus genome sequence of 2.55Gb and annotated 22,487 genes. Comparative genomic analysis reveals specific gene family expansions or reductions that are associated with the formation of adhesive setae, nocturnal vision and tail regeneration, as well as the diversification of olfactory sensation. The obtained genomic data provide robust genetic evidence of adaptive evolution in reptiles.
    No preview · Article · Nov 2015 · Nature Communications
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    ABSTRACT: Calpain 3 (CAPN3), also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA) of gastrocnemius muscle were decreased gradually from 1-14 days and then recovery from 14-28 days. The active form of CAPN3 (~62 kDa) protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA) injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury.
    Preview · Article · Nov 2015 · International Journal of Molecular Sciences
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    ABSTRACT: The regeneration-competent adult animals have ability to regenerate their lost complex appendages with a near-perfect replica, owing to the positional identity acquired by the progenitor cells in the blastema, i.e. the blastemal cells. CD59, a CD59/Ly6 family member, has been identified as a regulator of positional identity in the tail blastemal cells of Gekko japonicus. To determine whether this function of CD59 is unique to the regenerative amniote(s) and how CD59 mediates PD axis patterning during tail regeneration, we examined its protective role on the complement-mediated cell lysis and intervened CD59 expression in the tail blastemal cells using an in vivo model of adenovirus transfection. Our data revealed that gecko CD59 was able to inhibit complement-mediated cell lysis. Meanwhile, CD59 functioned on positional identity through expression in cartilage precursor cells. Intervening positional identity by overexpression or siRNA knockdown of CD59 resulted in abnormal cartilaginous cone patterning due to the decreased differentiation of blastemal cells to cartilage precursor cells. The cartilage formation-related genes were found to be under the regulation of CD59. These results indicate that CD59, an evolutionarily transitional molecule linking immune and regenerative regulation, affects tail regeneration by mediating cartilage patterning.
    No preview · Article · Aug 2015 · Scientific Reports

  • No preview · Article · Apr 2015 · Molecular Therapy
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    ABSTRACT: Natural polysaccharides are biomaterials widely used for constructing scaffolds in tissue engineering. While natural polysaccharides have been shown to robustly promote tissue regeneration, the underlying molecular mechanism remains largely unknown. Here, we show that chitooligosaccharides (COS), the intermediate products of chitosan degradation, stimulate peripheral nerve regeneration in rats. Our experiment also shows that COS stimulate the proliferation of Schwann cells (SCs) during nerve regeneration. By analyzing the transcriptome and gene regulatory network, we identified the miR-27a/FOXO1 axis as the main signaling pathway for mediating the proliferative effects of COS on SCs. COS increase the expression level of miR-27a and cause a reduction of FOXO1, which subsequently accelerates the cell cycle and stimulates SC proliferation to stimulate nerve regeneration. These findings define a basic pathway for oligosaccharides-mediated cell proliferation and reveal a novel aspect of polysaccharide biomaterials in tissue engineering.
    No preview · Article · Nov 2014 · Molecular Neurobiology
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    ABSTRACT: Peripheral nerve injury is a common clinical problem. Nerve growth factor (NGF) promotes peripheral nerve regeneration, but its clinical applications are limited by several constraints. In this study we found that the time-dependent expression profiles of eight let-7 family members in the injured nerve after sciatic nerve injury were roughly similar to each other. Let-7 microRNAs (miRNAs) significantly reduced cell proliferation and migration of primary Schwann cells (SCs) by directly targeting NGF and suppressing its protein translation. Following sciatic nerve injury, the temporal change in let-7 miRNA expression was negatively correlated with that in NGF expression. Inhibition of let-7 miRNAs increased NGF secretion by primary cultured SCs and enhanced axonal outgrowth from a co-culture of primaty SCs and dorsal root gangalion neurons. In vivo tests indicated that let-7 inhibition promoted SCs migration and axon outgrowth within a regenerative microenvironment. In addition, the inhibitory effect of let-7 miRNAs on SCs apoptosis might serve as an early stress response to nerve injury, but this effect seemed to be not mediated through a NGF-dependent pathway. Collectively, our results provide a new insight into let-7 miRNA regulation of peripheral nerve regeneration and suggest a potential therapy for repair of peripheral nerve injury.Molecular Therapy (2014); doi:10.1038/mt.2014.220.
    Preview · Article · Nov 2014 · Molecular Therapy
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    ABSTRACT: The Wingless/Integrated (Wnt) signaling pathway plays important roles in central nervous system (CNS) development and regeneration, and β-catenin, the central component, has been considered in association with adult neurogenesis. To decipher its roles on spontaneous spinal cord regeneration, we cloned β-catenin from Gekko japonicus and examined its function in regenerating spinal cord. The protein was localized in the neurons and oligodendrocytes and maintained a stable expression levels during the spinal cord regeneration. The temporal pattern of expression has been found to be completely distinct with those of glycogen synthase kinase 3β (GSK3β). Experiments of gain-of-function by overexpression of full length β-catenin or stabilized ΔN90-β-catenin revealed that the accumulated protein attenuates the elongation of neurites and oligodendrocyte process. Knockdown of endogenous β-catenin, however, decreased proliferation of oligodendrocytes by affecting expression of downstream lef1 and c-jun. The upregulated extracellular matrix fibronectin in injured cord was found to be inefficient in regulation of β-catenin expression. Our results suggest that a tightly regulated stable expression of β-catenin is required for the spontaneous spinal cord regeneration.
    No preview · Article · Sep 2014 · Journal of Molecular Neuroscience
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    ABSTRACT: In order to investigate the influence of different heavy metal ions on the formation of the oxyfluoride glasses and glass ceramics, samples with different PbF2/CdF2 ratios have been prepared by the melting quenching and thermal treatment method. The different effects of Pb2+ and Cd2+ on the glass network structure are investigated by FTIR and Raman spectra. During the formation of glass network structure, Pb2+ prefers to break the Si–O–Si bond and subsequently bond to F– for charge compensation, and Cd2+ prefers to break the Si–O–Al bond and is surrounded by O2–. Pb2+ and F– gather together and form the fluoride nanocrystals, while Cd2+ remains in oxide matrix after thermal treatment. Introduction of proper CdF2 is important to adjust and control the glass network structure and crystallization process in the fabrication of the transparent glass ceramics.
    No preview · Article · May 2014 · Journal of Materials Science and Technology -Shenyang-
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    ABSTRACT: Bone marrow mesenchymal stem cells (MSCs) can be differentiate towards a Schwann cells (SCs) lineage when exposed to pre-inducing reagents β-mercaptoethanol (BME) and retinoic acid (RA), followed by inducing factors: forskolin (FSK), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), and heregulin (HRG). However, the underlying mechanisms remain unclear. Here, we investigated the individual effects of these inducing factors on the differentiation of MSCs towards SC phenotype in rats. We show that the omission of either HRG or PDGF from the induction medium is not sufficient to change the SC-like phenotype or the expression level of the SC marker, S100β. However, the omission of bFGF from the induction medium effectively blocked neural induction of the MSCs. Moreover, only bFGF was found to inhibit MSC proliferation during differentiation. To clarify the mechanism responsible for the effect of bFGF, we also investigated the activation of the extracellular signal-regulated kinase (ERK) pathway in the induced cells. Our results suggest that morphological changes in MSCs induced by bFGF depend on the activation of ERK, and bFGF may be an indispensable factor that induces MSCs to differentiate into cells with SCs phenotype.
    No preview · Article · Dec 2013 · Neuroscience Letters
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    ABSTRACT: Uncontrolled, excessive inflammation contributes to the secondary tissue damage of traumatic spinal cord, and HMGB1 is highlighted for initiation of a vicious self-propagating inflammatory circle by release from necrotic cells or immune cells. Several regenerative-competent vertebrates have evolved to circumvent the second damages during the spontaneous spinal cord regeneration with an unknown HMGB1 regulatory mechanism. By genomic surveys, we have revealed that HMGB1 two paralogs are broadly retained from fish onwards in the phylogeny. However, their spatial-temporal expression and effects, as shown in lowest amniote gecko, were tightly controlled in order that limited inflammation was produced in spontaneous regeneration. Gecko HMGB1 (gHMGB1) two paralogs yielded distinct injury and infectious responses, with gHMGB1b significantly upregulated in the injured cord. The intracellular gHMGB1b induced less release of inflammatory cytokines than gHMGB1a in macrophages, and the effects could be shifted by exchanging one amino acid in the inflammatory domain. Both intracellular proteins were able to mediate neuronal programmed apoptosis, which has been indicated to produce negligible inflammatory responses. In vivo studies demonstrated that the extracellular proteins could not trigger a cascade of the inflammatory cytokines in the injured spinal cord. Signal transduction analysis found that the recombinant proteins could not bind with cell surface receptors TLR2 and TLR4 to activate inflammatory signaling pathway. However they were able to interact with RAGE to potentiate oligodendrocytes migration by activation of both NFκB and Rac1/Cdc42 signaling. Our results reveal that HMGB1 does not mediate the inflammatory response in spontaneous spinal cord regeneration, but promotes CNS regeneration.
    No preview · Article · May 2013 · Journal of Biological Chemistry
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    ABSTRACT: The enolase2 gene is usually expressed in mature neurons and also named neuron specific enolase (NSE). In the present study, we first obtained the NSE gene cDNA sequence by using the RACE method based on the expressed sequence tag (EST) fragment from the cDNA library of Gekko japonicus and identified one transcript of about 2.2 kb in central nervous system of Gekko japonicus by Northern blotting. The open reading frame of NSE is 1305 bp, which encodes a 435 amino-acid protein. We further investigated the multi-tissue expression pattern of NSE by RT-PCR and found that the expression of NSE mRNA was very high in brain, spinal cord and low in heart, while it was not detectable in other tissues. The real-time quantitative PCR was used to investigate the time-dependent change in the expression of the NSE mRNA level after gecko spinal cord transection and found it significantly increased at one day, reaching its highest level three days post-injury and then decreasing at the seventh day of the experiment. The recombinant plasmid of pET-32a-NSE was constructed and induced to express His fused NSE protein. The purified NSE protein was used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65536 determined by ELISA. Western blotting showed that the prepared antibody could specifically recognize the recombinant and endogenous NSE protein. The result of immunohistochemistry revealed that positive signals were present in neurons of the brain and the spinal cord. This study provided the tools of cDNA and polyclonal antibody for studying NSE function in Gekko japonicus.
    Full-text · Article · May 2013 · International Journal of Molecular Sciences
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    ABSTRACT: Gekko japonicus undergoes dramatic changes in the caudal spinal cord after tail amputation. The amputation induces cell proliferation in the caudal ependymal tube. We performed hematoxylin and eosin staining at different time points in the regeneration process to investigate the morphological characterization of the regenerated appendages. The central canal extended to the blastema post-amputation and the cartilage and muscle tissue appeared 3 weeks after injury. We performed the bromodeoxyuridine (BrdU) incorporation assay to detect proliferating cells during the regeneration process. BrdU positive cells were detected in the peri-central canal. Furthermore, nestin and neuron-specific enolase (NSE) immunocytochemistry were applied to detect neural stem/progenitor cells and neurons. Two weeks after injury, nestin-positive cells undergoing proliferation were located outside of the ependymal tube, and NSE positive cells appeared after 3 weeks of amputation. These data suggest that neurogenesis is an early event during caudal spinal cord regeneration in gecko.
    No preview · Article · Nov 2012 · Journal of molecular histology
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    ABSTRACT: SNARE complex mediates cellular membrane fusion events essential for neurotransmitter release and synaptogenesis. SNAP25, a member of the SNARE proteins, plays critical roles during the development of the central nervous system via regulation by alternative splicing and protein kinase phosphorylation. To date, little information is available regarding the protein in the spinal cord regeneration, especially for the postnatal highly expressed isoform SNAP25b. In the present study, we characterized gecko SNAP25b, which shared high identity with those of other vertebrates. Expression of gecko SNAP25b was temporally upregulated in both neurons of spinal cord and forming ependymal tube following tail amputation, coinciding with the occurrence of regenerate re-innervation. Overexpression of gecko wild type SNAP25b in the SH-SY5Y and undifferentiated PC12 cells promoted the elongation and outgrowth of neurites, while mutant constructs at Serine(187) resulted in differential effects for which S187A had a promoting role. Knockdown of endogenous SNAP25b affected the formation of neurites, which could be rescued by overexpression of SNAP25b. FM1-43 staining revealed that transfection of S187E mutant construct reduced the recruitment of vesicles. In addition, transfection of gecko SNAP25b in the astrocyte, which is absent from neuronal specific VAMP2, was capable of enhancing process elongation, indicating a potential for various alternative protein combinations. Taken together, our data suggest that gecko SNAP25b is involved in spinal cord regeneration by promoting outgrowth and elongation of neurites in a more extensive protein binding manner.
    No preview · Article · Sep 2012 · The international journal of biochemistry & cell biology

  • No preview · Article · Sep 2012 · The Journal of Dermatology
  • Jing Li · Yong Qin · Yun Gu · Yan Liu · Mei Liu
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    ABSTRACT: The tubulin beta III (TUBB3) gene encodes a class III member of the beta tubulin protein family that is primarily expressed in neurons and is considered to play a critical role in proper axon guidance and maintenance. This protein is generally used as a specific marker of neurons in the central nervous system. We obtained the full length cDNA sequence of TUBB3 by using the RACE method based on the EST fragment from the brain and spinal cord cDNA library of Gekko japonicus. We further investigated the multi-tissue expression pattern by RT-PCR and identified one transcript of TUBB3 about 1.8 kb in the central nervous system of Gekko japonicus by Northern blotting. The completed cDNA of gecko TUBB3 is 1 790 bp with an open reading frame of 1 350 bp, encoding a 450 amino-acid protein. The recombinant plasmid of pET-32a-TUBB3 was constructed and induced to express His-tagged TUBB3 protein in prokaryotic BL21 cells. The purified TUBB3 protein was then used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65 536 determined by ELISA. The result of western blotting showed that the TUBB3 antibody could specifically recognize the recombinant TUBB3 protein and endogenous TUBB3 protein. Our findings provide the tools to further understand the TUBB3 gene and investigate the regeneration of the central nervous system in Gekko japonicas.
    No preview · Article · Aug 2012 · Zoological Research
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    ABSTRACT: Solid tissues in the body possess a range of stiffness and provide cells with an instructive microenvironment. Scaffolds in tissue engineering should be rationally designed to become an adhesion substrate friendly to cells. Schwann cells are the principal glial cell in the peripheral nervous system and used as support cells for generating tissue-engineered nerve grafts. Although an important mechanical cue, substrate stiffness, has been documented to make significant effects on many types of cells cultured on the substrate, such a study for Schwann cells is still lacking. In this study, we investigated cell adhesion, survival, proliferation, migration, cytoskeleton, and neurotrophic actions of Schwann cells cultured on polyacrylamide gel substrates with different stiffness, and determined an optimal elastic modulus value for these substrates. Our data not only highlight the importance of substrate stiffness in the crosstalk between Schwann cells and surrounding microenvironment, but also introduce a new parameter, in addition to biocompatibility, biodegradability, and neuroaffinity, for designing scaffolds in nerve tissue engineering.
    No preview · Article · Jun 2012 · Biomaterials
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    ABSTRACT: GSK-3β signaling is involved in regulation of both neuronal and glial cell functions, and interference of the signaling affects central nervous system (CNS) development and regeneration. Thus, GSK-3β was proposed to be an important therapeutic target for promoting functional recovery of adult CNS injuries. To further clarify the regulatory function of the kinase on the CNS regeneration, we characterized gecko GSK-3β and determined the effects of GSK-3β inactivation on the neuronal and glial cell lines, as well as on the gecko tail (including spinal cord) regeneration. Gecko GSK-3β shares 91.7-96.7% identity with those of other vertebrates, and presented higher expression abundance in brain and spinal cord. The kinase strongly colocalized with the oligodendrocytes while less colocalized with neurons in the spinal cord. Phosphorylated GSK-3β (pGSK-3β) levels decreased gradually during the normally regenerating spinal cord ranging from L13 to the 6th caudal vertebra. Lithium injection increased the pGSK-3β levels of the corresponding spinal cord segments, and in vitro experiments on neurons and oligodendrocyte cell line revealed that the elevation of pGSK-3β promoted elongation of neurites and oligodendrocyte processes. In the normally regenerate tails, pGSK-3β kept stable in 2 weeks, whereas decreased at 4 weeks. Injection of lithium led to the elevation of pGSK-3β levels time-dependently, however destructed the regeneration of the tail including spinal cord. Bromodeoxyuridine (BrdU) staining demonstrated that inactivation of GSK-3β decreased the proliferation of blastemal cells. Our results suggested that species-specific regulation of GSK-3β was indispensable for the complete regeneration of CNS.
    No preview · Article · Jun 2012 · Journal of Cellular Biochemistry
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    Hua Yu · Hui Guo · Ming Zhang · Yan Liu · Min Liu · Li-Juan Zhao
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    ABSTRACT: It has been an open question whether Nd3+ ions are incorporated into the crystalline phase in oxyfluoride glass ceramics or not. Moreover, relative research has indicated that spectra characters display minor differences between before and after heat treatment in oxyfluoride glass compared to similar Er3+-, Yb3+-, Tm3+-, Eu3+-, etc.-doped materials. Here, we have studied the distribution of Nd3+ ions in oxyfluoride glass ceramics by X-ray diffraction quantitative analysis and found that almost none of the Nd3+ ions can be incorporated into the crystalline phase. In order to confirm the rationality of the process, the conventional mathematical calculation and energy-dispersive spectrometry line scanning are employed, which show good consistency. The distribution of Nd3+ ions in oxyfluoride glass ceramics reported here is significant for further optical investigations and applications of rare-earth doped oxyfluoride glass ceramics.
    Preview · Article · May 2012 · Nanoscale Research Letters
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    ABSTRACT: The growth-associated protein 43 (GAP-43) gene of Gekko japonicus was obtained from a brain and spinal cord cDNA library. The results of northern blot analysis showed the gecko GAP-43 gene transcript is 1.7 kb in length, and it was abundantly expressed in tissues of brain, spinal cord and ovary. Gecko GAP-43 promoted the outgrowth of Gsn3 cells and PC12 cell in vitro, and phosphorylation at serine 42 modulated the effect of GAP-43 on cell spreading and morphology. The change in GAP-43 expression in the spinal cord after tail amputation was examined by reverse transcription polymerase chain reaction (RT-PCR). The level of GAP-43 in the spinal cord was increased during the time course we examined, indicating a possible correlation between GAP-43 expression and the spinal cord injury and regeneration.
    No preview · Article · Mar 2012 · Molecular Biology Reports

Publication Stats

261 Citations
143.85 Total Impact Points


  • 2006-2015
    • Nantong University
      Tungchow, Jiangsu, China
  • 2012-2014
    • Nankai University
      • Department of Physics
      T’ien-ching-shih, Tianjin Shi, China
  • 2006-2012
    • Xi'an Jiaotong University
      • Department of Dermatology
      Ch’ang-an, Shaanxi, China
  • 2009-2011
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China