Zinc-ZIP8-MTF1信号通路调控骨性关节炎发生、发展及中医药作用机制的研究进展

综述锌离子-锌离子转运蛋白8-金属调节转录因子1(Zinc-ZIP8-MTF1)信号通路调控骨性关节炎发生发展及中医药作用机制的研究进展。Zn^2+稳态、锌转运蛋白以及锌离子依赖性转录因子与软骨损伤密切相关,Zinc-ZIP8-MTF1信号通路可调控骨性关节炎的发生、发展。目前中医药领域的相关研究局限于对Zn^2+水平的调控,未涉及对ZIP8和MTF1的影响,因此研究中医药对Zinc-ZIP8-MTF1信号通路的影响对治疗骨性关节炎有重要意义。

基于Zinc-ZIP8-MTF1轴研究独活寄生汤治疗膝骨关节炎的作用机制

目的观察独活寄生汤调控Zinc-ZIP8-MTF1轴,探讨独活寄生汤治疗膝骨关节炎的作用机制。方法选用54只小鼠,分为独活寄生汤组(DHJST组)、对照组(Model组)、空白组(Control组),每组18只,Model组、DHJST组构建小鼠膝骨关节炎模型,DHJST组予独活寄生汤,另两组予生理盐水,观察小鼠膝关节软骨病理改变,检测软骨细胞内Zn^(2+)浓度及锌转运蛋白(ZIP8、ZNT9)、金属调节转录因子(MTF1)、基质金属蛋白酶-3(MMP3)、基质金属蛋白酶-13(MMP13)表达。结果与Model组比较,DHJST组小鼠软骨组织病理学评分明显下降,软骨细胞内Zn^(2+)含量大幅减少,软骨组织中ZIP8、ZNT9、MTF1、MMP3、MMP13 mRNA表达降低(P<0.05)。结论Zinc-ZIP8-MTF1轴在独活寄生汤治疗KOA的机制中发挥了一定作用,但独活寄生汤对Zn2+进出软骨细胞的关键环节没有明显影响。

The IL-1R/TLR signaling pathway is essential for efficient CD8+ T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model

The outcome of hepatitis B viral(HBV)infection is determined by the complex interactions between replicating HBV and the immune system.While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively,the contribution of innate immune mechanisms remains to be defined.Here we examined the role of the interleukin-1 receptor/Toll-like receptor(IL-1R/TLR)signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model.Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice(WT)and a panel of mouse strains lacking specific innate immunity component expression.We found higher levels of HBV protein production and replication in Tlr2^(?/?),Tlr23479^(?/?),3d/Tlr24^(?/?),Myd88/Trif^(?/?)and Irak4^(?/?)mice,which was associated with reduced HBV-specific CD8+T-cell responses in these mice.Importantly,HBV clearance was delayed for more than 2 weeks in 3d/Tlr24^(?/?),Myd88/Trif^(?/?)and Irak4^(?/?)mice compared to WT mice.HBV-specific CD8+T-cell responses were functionally impaired for producing the cytokines IFN-γ,TNF-αand IL-2 in TLR signaling-deficient mice compared to WT mice.In conclusion,the IL-1R/TLR signaling pathway might contribute to controlling HBV infection by augmenting HBV-specific CD8+T-cell responses.

Ufl1 deficiency causes kidney atrophy associated with disruption of endoplasmic reticulum homeostasis

The UFMylation modification is a novel ubiquitin-like conjugation system,consisting of UBA5(E1),UFC1(E2),UFL1(E3),and the conjugating molecule UFM1.Deficiency in this modification leads to embryonic lethality in mice and diseases in humans.However,the function of UFL1 is poorly characterized.Studies on Ufl1 conditional knockout mice have demonstrated that the deletion of Ufl1 in cardiomyocytes and in intestinal epithelial cells causes heart failure and increases susceptibility to experimentally induced colitis,respectively,suggesting an essential role of UFL1 in the maintenance of the homeostasis in these organs.Yet,its physiological function in other tissues and organs remains completely unknown.In this study,we generate the nephron tubules specific Ufl1 knockout mice and find that the absence of Ufl1 in renal tubular results in kidney atrophy and interstitial fibrosis.In addition,Ufl1 deficiency causes the activation of unfolded protein response and cell apoptosis,which may be responsible for the kidney atrophy and interstitial fibrosis.Collectively,our results have demonstrated the crucial role of UFL1 in regulating kidney function and maintenance of endoplasmic reticulum homeostasis,providing another layer of understanding kidney atrophy.

Origin and Evolution of Core Components Responsible for Monitoring Light Environment Changes during Plant Terrestrialization

Light serves as the source of energy as well as an information signal for photosynthetic plants. During evolution, plants have acquired the ability to monitor environmental light radiation and adjust their developmental patterns to optimally utilize light energy for photosynthesis. The mechanisms of light perception and signal transduction have been comprehensively studied in past decades, mostly in a few model plants, including Arabidopsis thaliana. However, systematic analyses of the origin and evolution of core components involved in light perception and signaling are still lacking. In this study, we took advantage of the recently sequenced genomes and transcriptomes covering all the main Archaeplastida clades in the public domain to identify orthologous genes of core components involved in light perception and signaling and to reconstruct their evolutionary history. Our analyses suggested that acclimation to different distribution of light quality in new environments led to the origination of specific light signaling pathways in plants. The UVR8 (UV Resistance Locus 8) signaling pathway originated during the movement of plants from the deeper sea to shallow water and enabled plants to deal with ultraviolet B light (UV-B). After acquisition of UV-B adaptation, origination of the phytochrome signaling pathway helped plants to colonize water surface where red light became the prominent light energy source. The seedling emergence pathway, which is mediated by a combination of light and phytohormone signals that orchestrate plant growth pattern transitions, originated before the emergence of seed plants. Although cryptochromes and some key components of E3 ubiquitin ligase systems already existed before the divergence of the plant and animal kingdoms, the coevolution and optimization of light perception and downstream signal transduction components, including key transcription factors and E3 ubiquitin ligase systems, are evident during plant terrestrialization.