巨噬细胞具有较强的可塑性与异质性,可针对不同信号刺激发生功能转化,如转化为经典激活M1型(即M1型极化)、选择性激活M2型(即M2型极化)等。巨噬细胞M1/M2型极化的途径较为广泛,涉及核因子-κB(nuclear factor-κB,NF-κB)/丝裂原活化蛋...巨噬细胞具有较强的可塑性与异质性,可针对不同信号刺激发生功能转化,如转化为经典激活M1型(即M1型极化)、选择性激活M2型(即M2型极化)等。巨噬细胞M1/M2型极化的途径较为广泛,涉及核因子-κB(nuclear factor-κB,NF-κB)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、白细胞介素-4(interleukin-4,IL-4)/信号转导与转录激活因子6(signal transduction and activator of transcription 6,STAT6)信号通路、Notch信号通路、无翼样糖蛋白/β-连环蛋白(Wnt/β-catenin)信号通路等。同时,巨噬细胞M1/M2型极化可不同程度地受到外泌体、代谢物、非编码RNA、电刺激、益生菌等的功能调节,其失衡与不同类型肝病的发生、发展关系密切。该文通过对该极化的作用机制进行梳理,发现巨噬细胞M1型极化在肝组织损伤、炎症反应及纤维化进程中起助推作用,巨噬细胞M2型极化则相反;其中,肝癌作为慢性肝病的晚期阶段,以巨噬细胞M2型极化增强、巨噬细胞M1型极化受损为特征。因此,该文关注巨噬细胞M1/M2型极化在不同类型肝病中的作用,以期能更好地确立巨噬细胞亚群靶向疗法。展开更多
Poly(ADP-ribose)polymerase family member 14(PARP14),which is an intracellular mono(ADP-ribosyl)transferase,has been reported to promote post-stroke functional recovery,but its role in spinal cord injury(SCI)remains un...Poly(ADP-ribose)polymerase family member 14(PARP14),which is an intracellular mono(ADP-ribosyl)transferase,has been reported to promote post-stroke functional recovery,but its role in spinal cord injury(SCI)remains unclear.To investigate this,a T10 spinal cord contusion model was established in C57BL/6 mice,and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression.We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury,accompanied by obvious neuronal apoptosis,severe neuroinflammation,and slight bone loss.Furthermore,PARP14 levels were elevated in microglia after SCI,PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia(anti-inflammatory phenotype)to M1-polarized microglia(pro-inflammatory phenotype)that may have been mediated by the signal transducers and activators of transcription(STAT)1/6 pathway.Next,microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γand interleukin-4,respectively.The results showed that PARP14 knockdown promoted microglia M1 polarization,accompanied by activation of the STAT1 pathway.In addition,PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway.In conclusion,these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.展开更多
文摘巨噬细胞具有较强的可塑性与异质性,可针对不同信号刺激发生功能转化,如转化为经典激活M1型(即M1型极化)、选择性激活M2型(即M2型极化)等。巨噬细胞M1/M2型极化的途径较为广泛,涉及核因子-κB(nuclear factor-κB,NF-κB)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、白细胞介素-4(interleukin-4,IL-4)/信号转导与转录激活因子6(signal transduction and activator of transcription 6,STAT6)信号通路、Notch信号通路、无翼样糖蛋白/β-连环蛋白(Wnt/β-catenin)信号通路等。同时,巨噬细胞M1/M2型极化可不同程度地受到外泌体、代谢物、非编码RNA、电刺激、益生菌等的功能调节,其失衡与不同类型肝病的发生、发展关系密切。该文通过对该极化的作用机制进行梳理,发现巨噬细胞M1型极化在肝组织损伤、炎症反应及纤维化进程中起助推作用,巨噬细胞M2型极化则相反;其中,肝癌作为慢性肝病的晚期阶段,以巨噬细胞M2型极化增强、巨噬细胞M1型极化受损为特征。因此,该文关注巨噬细胞M1/M2型极化在不同类型肝病中的作用,以期能更好地确立巨噬细胞亚群靶向疗法。
基金supported by the Shenyang Science and Technology Project,No.20-205-4-092(to AHX)。
文摘Poly(ADP-ribose)polymerase family member 14(PARP14),which is an intracellular mono(ADP-ribosyl)transferase,has been reported to promote post-stroke functional recovery,but its role in spinal cord injury(SCI)remains unclear.To investigate this,a T10 spinal cord contusion model was established in C57BL/6 mice,and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression.We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury,accompanied by obvious neuronal apoptosis,severe neuroinflammation,and slight bone loss.Furthermore,PARP14 levels were elevated in microglia after SCI,PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia(anti-inflammatory phenotype)to M1-polarized microglia(pro-inflammatory phenotype)that may have been mediated by the signal transducers and activators of transcription(STAT)1/6 pathway.Next,microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γand interleukin-4,respectively.The results showed that PARP14 knockdown promoted microglia M1 polarization,accompanied by activation of the STAT1 pathway.In addition,PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway.In conclusion,these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.
