椎间盘由髓核、纤维环和软骨终板组成,对维持脊柱正常生理功能至关重要。椎间盘退变(intervertebral disc degeneration,IDD)是导致腰背痛等脊柱退行性疾病的主要病理基础,给人们的健康状况造成极大的困扰。然而目前对IDD的分子机制仍...椎间盘由髓核、纤维环和软骨终板组成,对维持脊柱正常生理功能至关重要。椎间盘退变(intervertebral disc degeneration,IDD)是导致腰背痛等脊柱退行性疾病的主要病理基础,给人们的健康状况造成极大的困扰。然而目前对IDD的分子机制仍然缺乏清晰的了解,导致缺乏有效的靶向干预措施。RAS同源家族成员A(RAS homolog family member A,RhoA)/Rho相关蛋白激酶(Rho-associated protein kinase,ROCK)信号通路是调节细胞收缩、迁移和生长的经典通路。其被激活后可参与调控细胞骨架重塑、细胞外基质代谢、生物钟节律、细胞表型改变、细胞衰老及死亡等环节,进而影响IDD的病理进程。深入探究RhoA/ROCK信号通路在IDD中的作用,不仅能揭示疾病发生的分子生物学机制,也有望为研发靶向该通路的治疗策略提供理论依据。展开更多
Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis ...Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis and development of HCs is crucial.Our current study highlights rhpn2,a member of rho-binding proteins,as essential for vestibular HC development.The rhpn2 gene is highly expressed in the crista and macula HCs.Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number,accompanied by vestibular dysfunction.Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants.Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab.Furthermore,co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA,validating the interaction of the two proteins.rhpn2 knockout leads to a decreased expression of rock2b,a canonical RhoA signaling pathway gene.Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants.This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway,providing a target for the treatment of balance disorders.展开更多
目的探究毛兰素(Erianin)在特应性皮炎(atopic dermatitis,AD)中的作用及其在高迁移率族蛋白1(high mobility group box-1,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)-Ras同源基因家族成员A(Ra...目的探究毛兰素(Erianin)在特应性皮炎(atopic dermatitis,AD)中的作用及其在高迁移率族蛋白1(high mobility group box-1,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)-Ras同源基因家族成员A(Ras homolog gene family member A,RhoA)/Rho关联含卷曲螺旋结合蛋白激酶1(recombinant Rho associated coiled coil containing protein kinase 1,ROCK1)信号通路中的调控机制。方法1-氯-2,4-二硝基苯(1-Chloro-2,4-dinitrobenzene,DNCB)诱导BALB/c小鼠作为AD的模型,测量小鼠的皮肤厚度、脾和淋巴结的重量。甲苯胺蓝和HE染色检测小鼠的背部皮肤和耳朵的病理改变;ELISA检测炎症因子水平;肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)刺激HaCaT细胞建立AD体外模型;采用流式细胞术检测细胞活性氧(reactive oxygen species,ROS);免疫荧光法检测线粒体活性氧(mitochondrion reactive oxygen species,mtROS);TUNEL检测细胞凋亡情况;免疫蛋白印迹法检测HMGB1、RAGE、RhoA、ROCK1蛋白表达情况。结果在体内实验中毛兰素抑制皮肤厚度的增加,减轻脾和淋巴结重量,改善炎症细胞的浸润和肥大细胞脱颗粒,降低炎症因子水平(P<0.05)。在体外实验中,毛兰素减少TNF-α诱导的HaCaT细胞ROS、mtROS的产生(P<0.01)。毛兰素治疗后HMGB1、RAGE、RhoA及ROCK1的蛋白表达量下降(P<0.01);使用RAGE特异性阻断剂(TFA)处理r-HMGB1刺激的HaCaT细胞后,HMGB1的表达没有发生变化,RAGE、RhoA及ROCK1表达减少(P<0.01);在Rho激酶抑制剂Y-27632+r-HMGB1组中,除RAGE的表达没有降低,其余结果与TFA+r-HMGB1组相近。结论毛兰素可能通过调节HMGB1/RAGE-RhoA/ROCK1信号通路缓解特应性皮炎。展开更多
The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,...The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,Vol.26,No.2,2018,pp.209–217.展开更多
文摘椎间盘由髓核、纤维环和软骨终板组成,对维持脊柱正常生理功能至关重要。椎间盘退变(intervertebral disc degeneration,IDD)是导致腰背痛等脊柱退行性疾病的主要病理基础,给人们的健康状况造成极大的困扰。然而目前对IDD的分子机制仍然缺乏清晰的了解,导致缺乏有效的靶向干预措施。RAS同源家族成员A(RAS homolog family member A,RhoA)/Rho相关蛋白激酶(Rho-associated protein kinase,ROCK)信号通路是调节细胞收缩、迁移和生长的经典通路。其被激活后可参与调控细胞骨架重塑、细胞外基质代谢、生物钟节律、细胞表型改变、细胞衰老及死亡等环节,进而影响IDD的病理进程。深入探究RhoA/ROCK信号通路在IDD中的作用,不仅能揭示疾病发生的分子生物学机制,也有望为研发靶向该通路的治疗策略提供理论依据。
基金supported by grants from the Natural Science Foundation of Jiangsu Province(BK20221377 and BK20220607)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(22KJB180023)the National Natural Science Foundation of China Grants(32200783,32350017,and 92368104),and the Qing Lan Project of Jiangsu Province.
文摘Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis and development of HCs is crucial.Our current study highlights rhpn2,a member of rho-binding proteins,as essential for vestibular HC development.The rhpn2 gene is highly expressed in the crista and macula HCs.Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number,accompanied by vestibular dysfunction.Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants.Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab.Furthermore,co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA,validating the interaction of the two proteins.rhpn2 knockout leads to a decreased expression of rock2b,a canonical RhoA signaling pathway gene.Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants.This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway,providing a target for the treatment of balance disorders.
文摘目的探究毛兰素(Erianin)在特应性皮炎(atopic dermatitis,AD)中的作用及其在高迁移率族蛋白1(high mobility group box-1,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)-Ras同源基因家族成员A(Ras homolog gene family member A,RhoA)/Rho关联含卷曲螺旋结合蛋白激酶1(recombinant Rho associated coiled coil containing protein kinase 1,ROCK1)信号通路中的调控机制。方法1-氯-2,4-二硝基苯(1-Chloro-2,4-dinitrobenzene,DNCB)诱导BALB/c小鼠作为AD的模型,测量小鼠的皮肤厚度、脾和淋巴结的重量。甲苯胺蓝和HE染色检测小鼠的背部皮肤和耳朵的病理改变;ELISA检测炎症因子水平;肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)刺激HaCaT细胞建立AD体外模型;采用流式细胞术检测细胞活性氧(reactive oxygen species,ROS);免疫荧光法检测线粒体活性氧(mitochondrion reactive oxygen species,mtROS);TUNEL检测细胞凋亡情况;免疫蛋白印迹法检测HMGB1、RAGE、RhoA、ROCK1蛋白表达情况。结果在体内实验中毛兰素抑制皮肤厚度的增加,减轻脾和淋巴结重量,改善炎症细胞的浸润和肥大细胞脱颗粒,降低炎症因子水平(P<0.05)。在体外实验中,毛兰素减少TNF-α诱导的HaCaT细胞ROS、mtROS的产生(P<0.01)。毛兰素治疗后HMGB1、RAGE、RhoA及ROCK1的蛋白表达量下降(P<0.01);使用RAGE特异性阻断剂(TFA)处理r-HMGB1刺激的HaCaT细胞后,HMGB1的表达没有发生变化,RAGE、RhoA及ROCK1表达减少(P<0.01);在Rho激酶抑制剂Y-27632+r-HMGB1组中,除RAGE的表达没有降低,其余结果与TFA+r-HMGB1组相近。结论毛兰素可能通过调节HMGB1/RAGE-RhoA/ROCK1信号通路缓解特应性皮炎。
文摘The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,Vol.26,No.2,2018,pp.209–217.
