Jianbing Qin

Nantong Medical College, Tungchow, Jiangsu Sheng, China

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Publications (23)53.31 Total impact

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    ABSTRACT: LIM-homeobox genes play a pivotal function in tissue patterning and differentiation, Lhx8 is a member of LIM-homeobox gene family, and it is selectively expressed in embryonic basal forebrain and is a key factor for the determination of cholinergic cells fate. However, besides cholinergic differentiation, little is known about the potential role of Lhx8 in cell biology. In this study, we transfected Lhx8 complementary DNA (cDNA) into PC12 cell line using lentiviral vectors to acquire the cells which stably expressed high level of Lhx8, and we provide the experimental evidence that overexpression of Lhx8 inhibits cell proliferation and induces cell cycle arrest but not apoptosis in vitro. In conclusion, besides cholinergic differentiation, our results suggest that Lhx8 also plays as a suppressor gene of proliferation in cell biology.
    In Vitro Cellular & Developmental Biology - Animal 12/2014; · 1.29 Impact Factor
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    ABSTRACT: Neural stem cells (NSCs) are pluripotent cells capable of differentiation into dopaminergic (DA) neurons, which are the major cell types damaged in Parkinson's disease (PD). Therefore, NSCs are considered the most promising cell source for cell replacement therapy of PD. However, the poor differentiation and maturation of DA neurons and decreased cell survival after transplantation are a challenge. We have previously demonstrated that Brn4, a member of the POU domain family of transcription factors, induced the differentiation of NSCs into neurons and promoted their maturation. In this study, we directly transduced tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis, into NSCs to induce DA neuronal differentiation. However, these DA neurons were morphologically immature and seldom expressed dopamine transporter (DAT), a late marker of mature DA neurons. In contrast, TH co-transfected with Brn4 generated increased number of mature DA neurons. Furthermore, Brn4 significantly induced the expression of glial cell line-derived neurotrophic factor (GDNF) with its receptors GFRα-1 and Ret, which may contribute to the maturation and survival of differentiated DA neurons. Our findings may be of future importance for the use of NSCs in cell replacement therapy of PD.
    Neuroscience Letters 04/2014; · 2.03 Impact Factor
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    ABSTRACT: Lycium barbarum is used both as a food additive and as a medicinal herb in many countries, and L. barbarum polysaccharides (LBPs), a major cell component, are reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer properties, and immune modulation. The effects of LBPs on neuronal function, neurogenesis, and drug-induced learning and memory deficits have not been assessed. We report the therapeutic effects of LBPs on learning and memory and neurogenesis in scopolamine (SCO)-treated rats. LBPs were administered via gastric perfusion for 2 weeks before the onset of subcutaneous SCO treatment for a further 4 weeks. As expected, SCO impaired performance in novel object and object location recognition tasks, and Morris water maze. However, dual SCO- and LBP-treated rats spent significantly more time exploring the novel object or location in the recognition tasks and had significant shorter escape latency in the water maze. SCO administration led to a decrease in Ki67- or DCX-immunoreactive cells in the dentate gyrus and damage of dendritic development of the new neurons; LBP prevented these SCO-induced reductions in cell proliferation and neuroblast differentiation. LBP also protected SCO-induced loss of neuronal processes in DCX-immunoreactive neurons. Biochemical investigation indicated that LBP decreased the SCO-induced oxidative stress in hippocampus and reversed the ratio Bax/Bcl-2 that exhibited increase after SCO treatment. However, decrease of BDNF and increase of AChE induced by SCO showed no response to LBP administration. These results suggest that LBPs can prevent SCO-induced cognitive and memory deficits and reductions in cell proliferation and neuroblast differentiation. Suppression of oxidative stress and apoptosis may be involved in the above effects of LBPs that may be a promising candidate to restore memory functions and neurogenesis.
    PLoS ONE 01/2014; 9(2):e88076. · 3.53 Impact Factor
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    ABSTRACT: Our previous studies indicated that transcription factor Brn-4 is upregulated in the surgically denervated hippocampus in vivo, promoting neuronal differentiation of hippocampal neural stem cells (NSCs) in vitro. The molecules mediating Brn-4 upregulation in the denervated hippocampus remain unknown. In this study we examined the levels of insulin-like growth factor-1 (IGF-1) in hippocampus following denervation. Surgical denervation led to a significant increase in IGF-1 expression in vivo. We also report that IGF-1 treatment on NSCs in vitro led to a marked acceleration of Brn-4 expression and cell differentiation down neuronal pathways. The promotion effects were blocked by PI3K-specific inhibitor (LY294002), but not MAPK inhibitor (PD98059); levels of phospho-Akt were increased by IGF-1 treatment. In addition, inhibition of IGF-1 receptor (AG1024) and mTOR (rapamycin) both attenuated the increased expression of Brn-4 induced by IGF-1. Together, the results demonstrated that upregulation of IGF-1 induced by hippocampal denervation injury leads to activation of the PI3K/Akt signaling pathway, which in turn gives rise to upregulation of the Brn-4 and subsequent stem cell differentiation down neuronal pathways.
    PLoS ONE 01/2014; 9(12):e113801. · 3.53 Impact Factor
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    ABSTRACT: The therapeutic potential of umbilical cord blood mesenchymal stem cells has been studied in several diseases. However, the possibility that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUCMSCs) can be used to treat neonatal hypoxic-ischemic encephalopathy (HIE) has not yet been investigated. This study focuses on the potential therapeutic effect of hUCMSC transplantation in a rat model of HIE. Dermal fibroblasts served as cell controls. HIE was induced in neonatal rats aged 7 days. hUCMSCs labeled with Dil were then transplanted into the models 24 hr or 72 hr post-HIE through the peritoneal cavity or the jugular vein. Behavioral testing revealed that hUCMSC transplantation but not the dermal fibroblast improved significantly the locomotor function vs. vehicle controls. Animals receiving cell grafts 24 hr after surgery showed a more significant improvement than at 72 hr. More hUCMSCs homed to the ischemic frontal cortex following intravenous administration than after intraperitoneal injection. Differentiation of engrafted cells into neurons was observed in and around the infarct region. Gliosis in ischemic regions was significantly reduced after hUCMSC transplantation. Administration of ganglioside (GM1) enhanced the behavioral recovery on the base of hUCMSC treatment. These results demonstrate that intravenous transplantation of hUCMSCs at an early stage after HIE can improve the behavior of hypoxic-ischemic rats and decrease gliosis. Ganglioside treatment further enhanced the recovery of neurological function following hUCMSC transplantation. © 2013 Wiley Periodicals, Inc.
    Journal of Neuroscience Research 01/2014; 92(1):35-45. · 2.97 Impact Factor
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    ABSTRACT: Lhx8 is a transcription factor for cholinergic differentiation. Our previous experiments found upregulation of Lhx8 promoted cholinergic neuronal differentiation of hippocampal neural stem/progenitor cells or hippocampal newborn neurons in vitro. However, the role of Lhx8 in VAChT expression and ACh release is still less understood. In this report, we transfected Lhx8 cDNA into neuronal cell line SHSY5Y by lentiviral vectors to acquire the cells which stably expressed high level of Lhx8. Using this cell model, we provided experimental evidence that increasing Lhx8 upregulated the expression of ChAT and VAChT, and also increased the ACh release in culture medium. We suggested that Lhx8 overexpression is a useful strategy to increase the release of ACh and maybe of therapeutic value to neurodegenerative diseases.
    Neuroscience Letters 12/2013; · 2.03 Impact Factor
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    ABSTRACT: Hippocampus is one of the neurogenesis areas in adult mammals, but the function of astrocytes in this area is still less known. In our previous study, the fimbria-fornix (FF)-transected hippocampal extracts promoted the proliferation and neuronal differentiation of radial glial cells in vitro. To explore the effects of hippocampal extracts on gliogenesis, the hippocampal astrocytes were treated by normal or ff-transected hippocampal extracts in vitro. The cells were immunostained by brain lipid-binding protein (BLBP), nestin, and SOX2 to assess their state of activation. The effects of astrocyte-conditioned medium on the neuronal differentiation of hippocampal neural stem cells (NSCs) were also investigated. After treatment of FF-transected hippocampal extracts, the number of BLBP, nestin, and Sox-positive cells were obviously more than the cells which treated by normal hippocampal extracts, these cells maintained a state of activation and the activated astrocyte-conditioned medium also promoted the differentiation of NSCs into more neurons. These findings suggest that the astrocytes can be activated by FF-transected hippocampal extracts and these activated cells also can promote the neuronal differentiation of hippocampal NSCs in vitro.
    In Vitro Cellular & Developmental Biology - Animal 11/2013; · 1.29 Impact Factor
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    ABSTRACT: Abstract CXCL12 and its physiologic receptor CXCR4 are involved in controlling cell survival, proliferation and migration in adult tissues. This study aimed to investigate the effects of CXCL12 on cortical neuron apoptosis in rats after traumatic brain injury (TBI) and the potential mechanisms involved. At 3 days after TBI, in situ terminal transferase d-UTP nick-end labeling assay (TUNEL) showed that the apoptotic index (AI) deceased significantly in the CXCL12 treatment group compared with the control group (p<0.05). Immunofluorescence double-labeled staining revealed that most of the TUNEL positive cells were NeuN positive neurons. The change trends of active caspase-3 expression were similar as those of the AI. The Bcl-2/Bax ratio was up-regulated in the CXCL12 group compared with the control group. However, the effect of CXCL12 could be partially reverted by the additional use of AMD3100 (a kind of antagonist of CXCR4) (p<0.05). Our results indicated that after TBI in rats CXCL12 combing CXCR4 receptors could inhibit the caspase-3 pathway by up-regulating Bcl-2/Bax ratio, which protect neurons from apoptosis.
    The International journal of neuroscience 08/2013; · 0.86 Impact Factor
  • In Vitro Cellular & Developmental Biology - Animal 02/2013; · 1.29 Impact Factor
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    ABSTRACT: Focal and diffuse neuronal loss happened after traumatic brain injury (TBI). With little in the way of effective repair, recent interest has focused on endogenic neural progenitor cells (NPCs) as a potential method for regeneration. Whether endogenic neural regeneration happened in the cortex of adult rat after TBI remains to be determined. In this study, rats were divided into a sham group and a TBI group, and the rat model of medium TBI was induced by controlled cortical impact. Rats were injected with BrdU at 1 to 7 days post-injury (dpi) to allow identification of differentiated cells and sacrificed at 1, 3, 7, 14 and 28 dpi for immunofluorescence. Results showed nestin(+)/sox-2(+) NPCs and GFAP(+)/sox-2(+) radial glial (RG)-like cells emerged in peri-injured cortex at 1, 3, 7, 14 dpi and peaked at 3 dpi. The number of GFAP(+)/sox-2(+) cells was less than that of nestin(+)/sox-2(+) cells. Nestin(+)/sox-2(+) cells from posterior periventricle (pPV) immigrated into peri-injured cortex through corpus callosum (CC) were found. DCX(+)/BrdU(+) newborn immature neurons in peri-injured cortex were found only at 3, 7, 14 dpi. A few MAP-2(+)/BrdU(+) newborn neurons in peri-injured cortex were found only at 7 and 14 dpi. NeuN(+)/BrdU(+) mature neurons were not found in peri-injured cortex at 1, 3, 7, 14 and 28 dpi. While GFAP(+)/BrdU(+) astrocytes emerged in peri-injured cortex at 1, 3, 7, 14, 28 dpi and peaked at 7 dpi then kept in a stable state. In the corresponding time point, the percentage of GFAP(+)/BrdU(+) astrocytes in BrdU(+) cells was more than that of NPCs or newborn neurons. No CNP(+)/BrdU(+) oligodendrocytes were found in peri-injured cortex. These findings suggest that NPCs from pPV and reactive RG-like cells emerge in peri-injured cortex of adult rats after TBI. It can differentiate into immature neurons and astrocytes, but the former fail to grow up to mature neurons.
    PLoS ONE 01/2013; 8(7):e70306. · 3.53 Impact Factor
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    ABSTRACT: Lhx8, also named L3, is a recently identified member of the LIM homeobox gene family. Previously, we found acetylcholinesterase (AChE)-positive cells in fimbria-fornix (FF) transected rat hippocampal subgranular zone (SGZ). In the present study, we detected choline acetyltransferase (ChAT)-positive cholinergic cells in hippocampal SGZ after FF transaction, and these ChAT-positive cells were double labeled by Lhx8. Then we overexpressed Lhx8 during neural differentiation of hippocampal neural stem/progenitor cells on adherent conditions using lentivirus Lenti6.3-Lhx8. The result indicated that overexpression of Lhx8 did not affect the proportion of MAP2-positive neurons, but increased the proportion of ChAT-positive cells in vitro. These results suggested that FF-transected hippocampal niche promoted the ChAT/Lhx8-positive cholinergic neurons generation in rodent hippocampus, and Lhx8 was not associated with the MAP2-positive neurons differentiation on adherent conditions, but played a role in the specification of cholinergic neurons derived from hippocampal neural stem/progenitor cells in vitro.
    In Vitro Cellular & Developmental Biology - Animal 11/2012; · 1.29 Impact Factor
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    ABSTRACT: Neural stem cells (NSCs) tranplantation has great potential for the treatment of neurodegenerative disease such as Parkinson's disease (PD). However, the usage of NSCs is limited because the differentiation of NSCs into specific dopaminergic neurons has proven difficult. We have recently demonstrated that transgenic expression of Nurr1 could induce the differentiation of NSCs into tyrosine hydroxylase (TH) immunoreactive dopaminergic neurons, and forced co-expression of Nurr1 with Brn4 caused a dramatic increase in morphological and phenotypical maturity of these neurons. In this study, we investigated the effect of transplanted NSCs in PD model rats. The results showed that overexpression of Nurr1 promoted NSCs to differentiate into dopaminergic neurons in vivo, increased the level of dopamine (DA) neurotransmitter in the striatum, resulting in behavioral improvement of PD rats. Importantly, co-expression of Nurr1 and Brn4 in NSCs significantly increased the maturity and viability of dopaminergic neurons, further raised the DA amount in the striatum and reversed the behavioral deficit of the PD rats. Our findings provide a new potential and strategy for the use of NSCs in cell replacement therapy for PD.
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 10/2012; · 2.03 Impact Factor
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    ABSTRACT: During the central nervous system (CNS) development, radial glia cells (RGCs) play at least two essential roles, they contribute to neuronal production and the subsequent guidance of neuronal migration, whereas its precise distribution and contribution to cerebral cortex remains less understood. In this research, we used Vimentin as an astroglial marker and Sox2 as a neural progenitor marker to identify and investigate RGCs in rat cerebral cortex at embryonic day (E) 16.5. We found that the Sox2+ progenitor cells localized in the germinal zone (GZ) of E16.5 cerebral cortex, ~95% Sox2+ cells co-localized with Vimentin+ or Nestin+ radial processes which extended to the pial surface across the cortical plate (CP). In vitro, we obtained RG-like cells from E16.5 cerebral cortex on adherent conditions, these Sox2+ Radial glia (RG)-like cells shared some properties with RGCs in vivo, and these Sox2+ RG-like cells could differentiate into astrocytes, oligodendrocytes and presented the radial glia-neuron lineage differentiation ability. Taken together, we identified and investigated some characterizations and properties of Sox2+ RGCs derived from E16.5 cerebral cortex, we suggested that the embryonic Sox2+ progenitor cells which located in the cortical GZ were mainly composed of Sox2+ RGCs, and the cortex-derived Sox2+ RG-like cells displayed the radial glia-neuron lineage differentiation ability as neuronal progenitors in vitro.
    Histochemie 09/2011; 136(5):515-26. · 2.61 Impact Factor
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    ABSTRACT: Successful neural stem cells (NSCs) therapies require the controlled differentiation of NSCs into neurons. Porous chitosan scaffold was explored if it promoted neuronal differentiation of NSCs in the presence of nerve growth factor (NGF) in 3-dimensional (3-D) culture. Chitosan scaffold was made by the freeze-drying technique. NSCs were cultured under four different conditions: on flat cover slips (2-D structure) in media with or without NGF, and on chitosan scaffold (3-D structure) in media with or without NGF. Immunohistochemical staining was used to observe multi-directional differentiation of cultured NSCs. Photomicrographs were taken and analyzed for cell number, soma size, and neuronal process length. The porosity index of chitosan scaffold was around 90% and the diameter of pores was 50-350 μm. NSCs could differentiate into neurons, astrocytes, and oligodendrocytes under all culture conditions. The rank efficacy for neuronal differentiation was 3-D culture with NGF group > 3-D culture without NGF group > 2-D culture with NGF group > 2-D culture without NGF group. The results suggest that the combination of chitosan scaffold and NGF exerts a synergistic effect on neuronal differentiation of NSCs, a requirement for successful integration into the damaged central nervous system.
    Neuro endocrinology letters 09/2011; 32(5):705-10. · 0.93 Impact Factor
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    ABSTRACT: The role of radial glia cells (RGCs) as neural progenitors and as guides for migrating neurons is well established, mouse or human-derived radial glia (RG)-like cells in vitro showed some astroglia and stem/progenitor properties like RGCs in vivo, but different species-derived RG-like cells present some different properties. Here we acquired rat-derived RG-like cells on adherent conditions in vitro and then identified their astroglia and stem/progenitor properties. Similarly to the RGCs, the RG-like cells could be double-labeled by brain lipid-binding protein, glial fibrillary acidic protein, vimentin with nestin and expressed some astroglia and stem/progenitor genes; these cells also presented tripotent differentiation potentialities, albeit the ability of gliogenesis far exceeded the neurogenesis in vitro. Taken together, we acquired and identified some properties of rat-derived RG-like cells from fetal cerebral cortices in vitro.
    In Vitro Cellular & Developmental Biology - Animal 05/2011; 47(7):431-7. · 1.29 Impact Factor
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    ABSTRACT: The role of radial glia cells (RGCs) as neural progenitors and as guides for migrating neurons is well established, whereas their precise contribution to adult hippocampal neurogenesis remains less understood. To precisely study the properties of hippocampal RGCs under normal conditions in vitro, here we acquired the hippocampal RGCs of postnatal 1 d rats under adherent conditions in vitro, identified their astroglia and stem/progenitor properties. We found that the neonatal rat hippocampal RGCs had longer processes than the RGCs from fetal cerebral cortices, and these cells could be double-labeled by BLBP, GFAP, Vimentin with Nestin and expressed some stem/progenitor genes, these cells also presented multiple differentiation potentialities, albeit the ability of gliogenesis far exceeded the neurogenesis under normal culture conditions in vitro. Taken together, we acquired and identified some properties of the RGCs from neonatal rat hippocampi in vitro.
    Neuroscience Letters 03/2011; 490(3):209-14. · 2.03 Impact Factor
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    ABSTRACT: Lesions to the fimbria fornix (FiFx) plus cingulate bundle (CB), the principal routes of communication of forebrain cholinergic regions, produce lasting impairment of spatial learning and memory in mice. We report that extensive neurogenesis takes place in the FiFx, CB, and basalis magnocellularis following FiFx plus CB transection. Immunofluorescence revealed that nestin-expressing cells were present in all 3 areas following lesion; the majority of nestin-positive cells were also positive for 5-bromo-2-deoxy-uridine, a marker of DNA synthesis. Nestin-positive proliferative cells were almost entirely absent from unlesioned tissue. Neurospheres cultured in vitro from lesioned FiFx displayed the characteristics of neural stem cells--proliferation, expression of embryonic markers, and multipotential differentiation into neurons, astrocytes, and oligodendrocytes. At early stages after transection, a small number of immature and migrating doublecortin-immunopositive neurons were detected in lesioned FiFx, where neuronal cell bodies are normally absent. At later stages, postlesion immature neurons developed into β-tubulin III-positive mature neurons. Lentivirus labeling assay implied that the injury-induced neurogenesis in FiFx may be from local neurogenic astrocytes but not from dentate gyrus. These results demonstrate that insult to cholinergic tracts can stimulate neural stem cell proliferation and neuronal regeneration not only in innervated regions but also in the projection pathways themselves. Ectopic neurogenesis in cholinergic system-related areas provides an additional mechanism for repair of cholinergic innervation following damage.
    Stem cells and development 12/2010; 20(9):1627-38. · 4.15 Impact Factor
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    ABSTRACT: Brn-4, a member of the homeobox family of transcription factors, has previously been implicated in the regeneration and repair of denervated striatum. We investigated the effects of Brn-4 on the differentiation and development of neural stem cells (NSCs) from E16 rat hippocampus. Immunocytochemistry revealed that extracts of deafferented hippocampus promoted neuronal differentiation to a greater extent than extracts from normal hippocampus. Deafferented extracts also promoted maturation of newborn neurons as reflected in changes in cell areas and perimeters, and enhanced Brn-4 expression in MAP-2 positive neurons. Suppression or overexpression of Brn-4 in NSCs markedly decreased or increased neuronal differentiation and maturation of newborn neurons, respectively. These results suggest that Brn-4 expression is required both for neuronal differentiation of NSCs and maturation of newborn neurons, and that there may be some regulatory factors in deafferented hippocampus that can regulate Brn-4 expression in neuronal progenitors. Brn-4 is therefore a potential research target for the development of new therapeutics to promote brain repair.
    Neuroscience Research 05/2010; 67(1):8-17. · 2.20 Impact Factor
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    ABSTRACT: Neurogenesis in the hippocampus continues throughout adult life and can be regulated by the local microenvironment. To determine whether denervation stimulates neurogenesis in hippocampus, proliferation, migration, and differentiation of local neural stem cells (NSCs) in dentate gyrus was investigated after fimbria fornix transection. In the denervated hippocampus, NSCs proliferated markedly and migrated along the subgranular layer, and more newborn cells differentiated into neurons or astrocytes. After denervation, more newborn cells in the deafferented hippocampus expressed Brn-4 and differentiated into beta-Tubulin III positive neurons. It is concluded that the local NSCs in hippocampus may proliferate and migrate into granule cell layer, in which changes in the deafferented hippocampus provided a suitable microenvironment for hippocampal neurogenesis and the increased Brn-4 in denervated hippocampus may be involved in this process.
    The International journal of neuroscience 03/2010; 120(3):192-200. · 0.86 Impact Factor
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    ABSTRACT: Hepatic stellate cell (HSC) activation is a key cellular event in the development of liver fibrosis. Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been shown to function as a key transcription regulator linked to suppressing HSC activation. Compelling evidence indicates that leptin plays a unique role in the development of liver fibrosis. The aim of this study is to investigate the in vivo impact of leptin on PPARgamma expression in HSCs in the model of TAA-induced liver damage. The results of the present study provide the first in vivo evidence that leptin might exert an inhibitory effect on PPARgamma protein expression in HSCs, which is mediated at least through leptin-induced ERK1/2 activation. Long-form leptin receptor is involved in leptin-induced ERK1/2 activation and the subsequent decline in PPARgamma expression in HSCs in the model. Furthermore, the inhibitory effect of leptin on PPARgamma protein expression enhances HSC activation and proliferation in this model. The in vivo findings from this report might provide additional insights into the mechanisms underlying the profibrogenic action of leptin in liver.
    Molecular and Cellular Endocrinology 03/2010; 323(2):193-200. · 4.04 Impact Factor