背景:类风湿关节炎是以持续性滑膜炎和进行性骨破坏为主要病理特征的慢性自身免疫性疾病。巨噬细胞作为关键的效应细胞,主要通过极化成不同功能表型,在类风湿关节炎发病机制中发挥核心作用。目的:综述巨噬细胞极化在类风湿关节炎骨破坏...背景:类风湿关节炎是以持续性滑膜炎和进行性骨破坏为主要病理特征的慢性自身免疫性疾病。巨噬细胞作为关键的效应细胞,主要通过极化成不同功能表型,在类风湿关节炎发病机制中发挥核心作用。目的:综述巨噬细胞极化在类风湿关节炎骨破坏中的作用及调控机制和最新治疗进展。方法:利用计算机检索Web of Science核心数据库、万方数据库和中国知网2005-2024年期间发表的相关文献。中文检索词为“巨噬细胞,类风湿关节炎,极化,骨与关节,软骨,自身免疫,炎症,M1巨噬细胞,M2巨噬细胞”,英文检索词为“macrophages,rheumatoid arthritis,polarization,bone and Joints,cartilage,autoimmunity,inflammation,M1 macrophage,M2 macrophage”,最终对53篇文献展开综述。结果与结论:类风湿关节炎是一种慢性炎症性疾病,以持续炎症性骨破坏为特征,如果治疗不当,可导致关节畸形,甚至功能丧失。巨噬细胞M1/M2极化比例失衡是类风湿关节炎疾病进展的关键点,这强调了研究巨噬细胞极化在类风湿关节炎炎症性骨破坏中的作用及调控机制的必要性,巨噬细胞极化调控机制能够作为新型治疗剂的潜在靶点。展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regul...The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.展开更多
In the article titled“Inhibiting SHP2 reduces glycolysis,promotes microglial M1 polarization,and alleviates secondary inflammation following spinal cord injury in a mouse model,”published in Neural Regeneration Rese...In the article titled“Inhibiting SHP2 reduces glycolysis,promotes microglial M1 polarization,and alleviates secondary inflammation following spinal cord injury in a mouse model,”published in Neural Regeneration Research(Ding et al.,2025),the title was incorrectly presented due to an error during the language polishing process.展开更多
文摘背景:类风湿关节炎是以持续性滑膜炎和进行性骨破坏为主要病理特征的慢性自身免疫性疾病。巨噬细胞作为关键的效应细胞,主要通过极化成不同功能表型,在类风湿关节炎发病机制中发挥核心作用。目的:综述巨噬细胞极化在类风湿关节炎骨破坏中的作用及调控机制和最新治疗进展。方法:利用计算机检索Web of Science核心数据库、万方数据库和中国知网2005-2024年期间发表的相关文献。中文检索词为“巨噬细胞,类风湿关节炎,极化,骨与关节,软骨,自身免疫,炎症,M1巨噬细胞,M2巨噬细胞”,英文检索词为“macrophages,rheumatoid arthritis,polarization,bone and Joints,cartilage,autoimmunity,inflammation,M1 macrophage,M2 macrophage”,最终对53篇文献展开综述。结果与结论:类风湿关节炎是一种慢性炎症性疾病,以持续炎症性骨破坏为特征,如果治疗不当,可导致关节畸形,甚至功能丧失。巨噬细胞M1/M2极化比例失衡是类风湿关节炎疾病进展的关键点,这强调了研究巨噬细胞极化在类风湿关节炎炎症性骨破坏中的作用及调控机制的必要性,巨噬细胞极化调控机制能够作为新型治疗剂的潜在靶点。
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金supported by grants from Simons Foundation (SFARI 479754),CIHR (PJT-180565)the Scottish Rite Charitable Foundation of Canada (to YL)funding from the Canada Research Chairs program。
文摘The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.
文摘In the article titled“Inhibiting SHP2 reduces glycolysis,promotes microglial M1 polarization,and alleviates secondary inflammation following spinal cord injury in a mouse model,”published in Neural Regeneration Research(Ding et al.,2025),the title was incorrectly presented due to an error during the language polishing process.
