Molting and metamorphosis are important physiological processes in insects that are tightly controlled by ecdysone receptor(EcR)through the 20-hydroxyecdysone(20E)signaling pathway.EcR is a steroid nuclear receptor(SR...Molting and metamorphosis are important physiological processes in insects that are tightly controlled by ecdysone receptor(EcR)through the 20-hydroxyecdysone(20E)signaling pathway.EcR is a steroid nuclear receptor(SR).Several FK506-binding proteins(FKBPs)have been identified from the mammal SR complex,and are thought to be involved in the subcellular trafficking of SR.However,their roles in insects are poorly understood.To explore whether FKBPs are involved in insect molting or metamorphosis,we injected an FKBP inhibitor(FK506)into a lepidopteran insect,Spodoptera litura,and found that molting was inhibited in 61.11%of the larvae,and that the time for larvae to pupate was significantly extended.A total of 10 FKBP genes were identified from the genome of s.litura and were clustered into 2 distinct groups,according to their subcellular localization,with FKBP13 and FKBP14 belonging to the endoplasmic reticulum(ER)group and with the other members belonging to the cytoplasmic(Cy)group.All the CyFKBPs were significantly upregulated in the prepupal or pupal stages,with the opposite being observed for the ER group members.FK506 completely blocked the transfer of EcR to the nucleus under 20E induction,and significantly downregulated the transcriptional expression of many 20E signaling genes.A similar phenomenon was observed after RNA interference of2 CyFKBPs(FKBP45 and FKBP12b),but not for FKBP13.Taken together,our data indicate that the cytoplasmic FKBPs,especially FKBP45 and FKBP12b,mediate the nuclear localization of EcR,thereby regulating the 20E signaling and ultimately affecting molting and metamorphosis in insects.展开更多
目的探讨FK506结合蛋白5(FK506-binding protein 5,FKBP5)基因多态性与小儿支气管哮喘易感性及糖皮质激素(glucocorticoid,GC)疗效的关系。方法选取2021-04/2023-04月作者医院收治的120例支气管哮喘患儿作为研究对象(哮喘组)。另外将同...目的探讨FK506结合蛋白5(FK506-binding protein 5,FKBP5)基因多态性与小儿支气管哮喘易感性及糖皮质激素(glucocorticoid,GC)疗效的关系。方法选取2021-04/2023-04月作者医院收治的120例支气管哮喘患儿作为研究对象(哮喘组)。另外将同时期来作者医院进行体检的150例健康儿童作为健康组。根据GC疗效不同将支气管哮喘患儿分为良好组(n=92)和不良组(n=28)。采用限制性片段长度多态性聚合酶链反应(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术鉴定FKBP5基因rs4713916位点基因分型。采用Hardy-Weinberg遗传平衡度检验对样本代表性进行评估。结果健康组和哮喘组FKBP5基因rs4713916位点基因型符合Hardy-Weinberg遗传平衡定律,样本具有代表性(P>0.05)。健康组FKBP5基因rs4713916位点TT(7.33%vs.18.33%)、TC(34.67%vs.37.50%)、CC(58.00%vs.44.17%)基因型频率和T(24.67%vs.37.08%)、C(75.33%vs.62.92%)等位基因频率与哮喘组比较差异有统计学意义(P均<0.05)。良好组FKBP5基因rs4713916位点TT(7.61%vs.53.57%)、TC(40.22%vs.28.57%)、CC(52.17%vs.17.86%)基因型频率和T(27.72%vs.67.86%)、C(72.28%vs.32.14%)等位基因频率与不良组比较差异有统计学意义(P均<0.05)。FKBP5基因rs4713916位点TT基因型患儿治疗前后第1秒用力呼气容积(forced expiratory volume in one second,FEV1)、用力肺活量(forced vital capacity,FVC)、FEV1/FVC的差值低于TC、CC基因型患儿,且TC基因型低于CC基因型(P均<0.05)。结论FKBP5基因rs4713916位点多态性与小儿支气管哮喘易感风险和GC疗效有关,且携带TT基因型患儿对GC治疗的敏感性更差。展开更多
基金supported by grants from the National Natural Science Foundation of China(grant no.32272523)the Natural Science Foundation of Guangdong Province,China(grant no.2023A1515010178)the Laboratory of Lingnan Modern Agriculture Project(grant no.NT2021003).
文摘Molting and metamorphosis are important physiological processes in insects that are tightly controlled by ecdysone receptor(EcR)through the 20-hydroxyecdysone(20E)signaling pathway.EcR is a steroid nuclear receptor(SR).Several FK506-binding proteins(FKBPs)have been identified from the mammal SR complex,and are thought to be involved in the subcellular trafficking of SR.However,their roles in insects are poorly understood.To explore whether FKBPs are involved in insect molting or metamorphosis,we injected an FKBP inhibitor(FK506)into a lepidopteran insect,Spodoptera litura,and found that molting was inhibited in 61.11%of the larvae,and that the time for larvae to pupate was significantly extended.A total of 10 FKBP genes were identified from the genome of s.litura and were clustered into 2 distinct groups,according to their subcellular localization,with FKBP13 and FKBP14 belonging to the endoplasmic reticulum(ER)group and with the other members belonging to the cytoplasmic(Cy)group.All the CyFKBPs were significantly upregulated in the prepupal or pupal stages,with the opposite being observed for the ER group members.FK506 completely blocked the transfer of EcR to the nucleus under 20E induction,and significantly downregulated the transcriptional expression of many 20E signaling genes.A similar phenomenon was observed after RNA interference of2 CyFKBPs(FKBP45 and FKBP12b),but not for FKBP13.Taken together,our data indicate that the cytoplasmic FKBPs,especially FKBP45 and FKBP12b,mediate the nuclear localization of EcR,thereby regulating the 20E signaling and ultimately affecting molting and metamorphosis in insects.
文摘目的探讨FK506结合蛋白5(FK506-binding protein 5,FKBP5)基因多态性与小儿支气管哮喘易感性及糖皮质激素(glucocorticoid,GC)疗效的关系。方法选取2021-04/2023-04月作者医院收治的120例支气管哮喘患儿作为研究对象(哮喘组)。另外将同时期来作者医院进行体检的150例健康儿童作为健康组。根据GC疗效不同将支气管哮喘患儿分为良好组(n=92)和不良组(n=28)。采用限制性片段长度多态性聚合酶链反应(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术鉴定FKBP5基因rs4713916位点基因分型。采用Hardy-Weinberg遗传平衡度检验对样本代表性进行评估。结果健康组和哮喘组FKBP5基因rs4713916位点基因型符合Hardy-Weinberg遗传平衡定律,样本具有代表性(P>0.05)。健康组FKBP5基因rs4713916位点TT(7.33%vs.18.33%)、TC(34.67%vs.37.50%)、CC(58.00%vs.44.17%)基因型频率和T(24.67%vs.37.08%)、C(75.33%vs.62.92%)等位基因频率与哮喘组比较差异有统计学意义(P均<0.05)。良好组FKBP5基因rs4713916位点TT(7.61%vs.53.57%)、TC(40.22%vs.28.57%)、CC(52.17%vs.17.86%)基因型频率和T(27.72%vs.67.86%)、C(72.28%vs.32.14%)等位基因频率与不良组比较差异有统计学意义(P均<0.05)。FKBP5基因rs4713916位点TT基因型患儿治疗前后第1秒用力呼气容积(forced expiratory volume in one second,FEV1)、用力肺活量(forced vital capacity,FVC)、FEV1/FVC的差值低于TC、CC基因型患儿,且TC基因型低于CC基因型(P均<0.05)。结论FKBP5基因rs4713916位点多态性与小儿支气管哮喘易感风险和GC疗效有关,且携带TT基因型患儿对GC治疗的敏感性更差。
