Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins ...Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.展开更多
Sox9在脊椎动物性腺分化及精巢发育中行使重要功能。为探究线纹海马sox9a的分子特征及表达模式,本研究采用RACE获得了其cDNA全长1979 bp,包含339 bp 5’ UTR、1488 bp的ORF和152 bp 3’ UTR,共编码496个氨基酸;氨基酸多重比对显示,线纹...Sox9在脊椎动物性腺分化及精巢发育中行使重要功能。为探究线纹海马sox9a的分子特征及表达模式,本研究采用RACE获得了其cDNA全长1979 bp,包含339 bp 5’ UTR、1488 bp的ORF和152 bp 3’ UTR,共编码496个氨基酸;氨基酸多重比对显示,线纹海马sox9具有高度保守的HMG-box结构域;系统进化树分析表明,其与侏儒海马sox9a的亲缘关系最近;RT-qPCR显示,sox9a泛在表达于线纹海马成体的主要组织中,在性腺中呈显著的雄性偏好性高表达于精巢,揭示其可能参与线纹海马精巢的分化及维持。本研究为后续深入研究线纹海马sox9a在性别发育中的功能奠定了基础。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81070996(to ZW),81572151(to XH)Shaanxi Provincial Key R&D Program,Nos.2020ZDLSF02-05(to ZW),2021ZDLSF02-10(to XH)+1 种基金Everest Project of Military Medicine of Air Force Medical University,No.2018RCFC02(to XH)Boosting Project of the First Affiliated Hospital of Air Force Medical University,No.XJZT19Z22(to ZW)。
文摘Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.
文摘Sox9在脊椎动物性腺分化及精巢发育中行使重要功能。为探究线纹海马sox9a的分子特征及表达模式,本研究采用RACE获得了其cDNA全长1979 bp,包含339 bp 5’ UTR、1488 bp的ORF和152 bp 3’ UTR,共编码496个氨基酸;氨基酸多重比对显示,线纹海马sox9具有高度保守的HMG-box结构域;系统进化树分析表明,其与侏儒海马sox9a的亲缘关系最近;RT-qPCR显示,sox9a泛在表达于线纹海马成体的主要组织中,在性腺中呈显著的雄性偏好性高表达于精巢,揭示其可能参与线纹海马精巢的分化及维持。本研究为后续深入研究线纹海马sox9a在性别发育中的功能奠定了基础。
