目的:检测传代后的视网膜色素上皮细胞(retinal pigment epithelial,RPE)MERTK基因表达的变化,明确传代的异体RPE移植的可行性。方法:离体培养原代的人视网膜色素上皮细胞,将原代细胞以1∶3比例进行传代至第6代,以SYBRGreen I real ti...目的:检测传代后的视网膜色素上皮细胞(retinal pigment epithelial,RPE)MERTK基因表达的变化,明确传代的异体RPE移植的可行性。方法:离体培养原代的人视网膜色素上皮细胞,将原代细胞以1∶3比例进行传代至第6代,以SYBRGreen I real time RT-PCR方法检测不同传代数的RPE细胞MERTK基因表达的水平,采用2-ΔΔCT方法计算定量PCR的数值进而比较各代MERTK基因表达的的变化。结果:原代及传代的RPE细胞均表达MERTK基因。第二代RPE细胞MERTK基因表达水平与原代相同,第3～6代RPE细胞MERTK基因表达水平均明显低于原代。结论:传代的RPE细胞可以作为异体视网膜色素上皮细胞移植的细胞来源,但以第二代的RPE细胞为最佳选择。展开更多
Disruption of the blood-spinal cord barrier(BSCB)is a critical event in the secondary injury following spinal cord injury(SCI).Mertk has been reported to play an important role in regulating inflammation and cytoskele...Disruption of the blood-spinal cord barrier(BSCB)is a critical event in the secondary injury following spinal cord injury(SCI).Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics.However,the specific involvement of Mertk in BSCB remains elusive.Here,we demonstrated a distinct role of Mertk in the repair of BSCB.Mertk expression is decreased in endothelial cells following SCI.Overexpression of Mertk upregulated tight junction proteins(TJs),reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis.Ultimately,this led to enhanced neural regeneration and functional recovery.Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk.These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.展开更多
Tyro3,Axl,and Mertk(TAM)receptors play multiple roles in a myriad of physiological and pathological processes,varying from promoting the phagocytic clearance of apoptotic cells,sustaining the immune and inflammatory h...Tyro3,Axl,and Mertk(TAM)receptors play multiple roles in a myriad of physiological and pathological processes,varying from promoting the phagocytic clearance of apoptotic cells,sustaining the immune and inflammatory homeostasis,maintaining the blood-brain barrier(BBB)integrity and central nervous system(CNS)homeostasis,to mediating cancer malignancy and chemoresistance.Growth arrest-specific protein 6(Gas6)and protein S(Pros1)are the two ligands that activate TAM receptors.Recently,TAM receptors have been reported to mediate cell entry and infection of multitudinous enveloped viruses in a manner called apoptotic mimicry.Moreover,TAM receptors are revitalized during viral entry and infection,which sequesters innate immune and inflammatory responses,facilitating viral replication and immune evasion.However,accumulating evidence have now proposed that TAM receptors are not required for the infection of these viruses in vivo.In addition,TAM receptors protect mice against the CNS infection of neuroinvasive viruses and relieve the brain lesions during encephalitis.These protective effects are achieved through maintaining BBB integrity,attenuating proinflammatory cytokine production,and promoting neural cell survival.TAM receptors also regulate the programmed cell death modes of virus-infected cells,which have profound impacts on the pathogenesis and outcome of infection.Here,we systematically review the functionalities and underlying mechanisms of TAM receptors and propose the potential application of TAM agonists to prevent severe viral encephalitis.展开更多
The TAM family of receptors is preferentially expressed by professional and non-professional phagocytes,including macrophages,dendritic cells and natural killer cells in the immune system,osteoclasts in bone,Sertoli c...The TAM family of receptors is preferentially expressed by professional and non-professional phagocytes,including macrophages,dendritic cells and natural killer cells in the immune system,osteoclasts in bone,Sertoli cells in testis,and retinal pigmental epithelium cells in the retina.Mutations in the Mertk single gene or in different combinations of the double or triple gene mutations in the same cell cause complete or partial impairment in phagocytosis of their preys;and as a result,either the normal apoptotic cells cannot be efficiently removed or the tissue neighbor cells die by apoptosis.This scenario of TAM regulation represents a widely adapted model system used by phagocytes in all different tissues.The present review will summarize current known functional roles of TAM receptors and their ligands,Gas 6 and protein S,in the regulation of phagocytosis.展开更多
基金National Natural Science Foundation of China(No.39800167)~~
文摘目的:检测传代后的视网膜色素上皮细胞(retinal pigment epithelial,RPE)MERTK基因表达的变化,明确传代的异体RPE移植的可行性。方法:离体培养原代的人视网膜色素上皮细胞,将原代细胞以1∶3比例进行传代至第6代,以SYBRGreen I real time RT-PCR方法检测不同传代数的RPE细胞MERTK基因表达的水平,采用2-ΔΔCT方法计算定量PCR的数值进而比较各代MERTK基因表达的的变化。结果:原代及传代的RPE细胞均表达MERTK基因。第二代RPE细胞MERTK基因表达水平与原代相同,第3～6代RPE细胞MERTK基因表达水平均明显低于原代。结论:传代的RPE细胞可以作为异体视网膜色素上皮细胞移植的细胞来源,但以第二代的RPE细胞为最佳选择。
基金Natural Science Foundation of Guangdong Province(2017A030313111)National Natural Science Foundation of China(81974329).
文摘Disruption of the blood-spinal cord barrier(BSCB)is a critical event in the secondary injury following spinal cord injury(SCI).Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics.However,the specific involvement of Mertk in BSCB remains elusive.Here,we demonstrated a distinct role of Mertk in the repair of BSCB.Mertk expression is decreased in endothelial cells following SCI.Overexpression of Mertk upregulated tight junction proteins(TJs),reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis.Ultimately,this led to enhanced neural regeneration and functional recovery.Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk.These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.
基金supported by the National Natural Science Foundation of China(81671971,81871641,81972979,U1902210 and U1602223)the Scientific Research Plan of the Beijing Municipal Education Committee(KM201710025002)+1 种基金the Key Project of Beijing Natural Science Foundation B(KZ201810025035)the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan(IDHT20190510)
文摘Tyro3,Axl,and Mertk(TAM)receptors play multiple roles in a myriad of physiological and pathological processes,varying from promoting the phagocytic clearance of apoptotic cells,sustaining the immune and inflammatory homeostasis,maintaining the blood-brain barrier(BBB)integrity and central nervous system(CNS)homeostasis,to mediating cancer malignancy and chemoresistance.Growth arrest-specific protein 6(Gas6)and protein S(Pros1)are the two ligands that activate TAM receptors.Recently,TAM receptors have been reported to mediate cell entry and infection of multitudinous enveloped viruses in a manner called apoptotic mimicry.Moreover,TAM receptors are revitalized during viral entry and infection,which sequesters innate immune and inflammatory responses,facilitating viral replication and immune evasion.However,accumulating evidence have now proposed that TAM receptors are not required for the infection of these viruses in vivo.In addition,TAM receptors protect mice against the CNS infection of neuroinvasive viruses and relieve the brain lesions during encephalitis.These protective effects are achieved through maintaining BBB integrity,attenuating proinflammatory cytokine production,and promoting neural cell survival.TAM receptors also regulate the programmed cell death modes of virus-infected cells,which have profound impacts on the pathogenesis and outcome of infection.Here,we systematically review the functionalities and underlying mechanisms of TAM receptors and propose the potential application of TAM agonists to prevent severe viral encephalitis.
基金This study was partially supported by NIH EY018830,RR017702,and RR018733Research to Prevent Blindnessand the National Natural Science Foundation of China(Grant Nos.30400229,30670643 and 30870788).
文摘The TAM family of receptors is preferentially expressed by professional and non-professional phagocytes,including macrophages,dendritic cells and natural killer cells in the immune system,osteoclasts in bone,Sertoli cells in testis,and retinal pigmental epithelium cells in the retina.Mutations in the Mertk single gene or in different combinations of the double or triple gene mutations in the same cell cause complete or partial impairment in phagocytosis of their preys;and as a result,either the normal apoptotic cells cannot be efficiently removed or the tissue neighbor cells die by apoptosis.This scenario of TAM regulation represents a widely adapted model system used by phagocytes in all different tissues.The present review will summarize current known functional roles of TAM receptors and their ligands,Gas 6 and protein S,in the regulation of phagocytosis.
