Our previous results proved that Jagged-1/Notch signaling inhibits the phenotypic transformation of naive CD4+T cells into Th22 induced by both IL-6 and TNF-α.The current study showed that this process was facilitate...
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Our previous results proved that Jagged-1/Notch signaling inhibits the phenotypic transformation of naive CD4+T cells into Th22 induced by both IL-6 and TNF-α.The current study showed that this process was facilitated by hsp90 knockdown or SNX2112 with the augment of il-22,ahr and arnt,the attenuation of hes-1 as well as the high productions of Th22 cytokines and CCR6,which could be reversed by Hsp90 overexpression or *** Jagged-1 or DAPT caused downregulation or upregulation of Th22 phenotype,no changes were observed at the levels of Hsp90 mRNA and ***,the inhibition or activation of Hsp90 was able to reduce or enhance downstream Hes-1 via interacting with NICD and *** in vivo overexpression of Hsp90 could suppress deviation of Th22,which were rescued by hsp90 *** data demonstrate that Hsp90 can stabilize NICD and AhR to boost Notch signaling transduction,suggesting that it regulates Notch signaling to mediate Th22 differentiation.
Th22 cells play a crucial part in pathogenesis of autoimmune diseases.H owever,little is known about a mechanistic process of regulating their *** this study,Jagged-1 signaling suppressed the deviation of naive CD4+T ...
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Th22 cells play a crucial part in pathogenesis of autoimmune diseases.H owever,little is known about a mechanistic process of regulating their *** this study,Jagged-1 signaling suppressed the deviation of naive CD4+T cells into Th22,which could be rescued by DAPT or hes-1 ***-1 contributed to the reduction of Th22 by lessening AHR level,but the knockdown of arnt or ahr could facilitate Th22 *** were the significant interactions among Hes-1,AHR level and ARNT,whereas their up-or down-stream relationships were confirmed by various ***-1 signaling markedly alleviated the joint swelling and clinical scores in the rheumatoid arthritis-bearing mice via the diminished Th22 with the inhibition of TNF-α and *** findings strongly indicate that the activated Jagged-1/Notch pathway suppresses the skewing of naive CD4T cells into Th22 to relieve rheumatoid arthritis through reduction of IL-22 and TNF-α by Hes-1/ARNT/AHR signaling.
目的通过体内外实验探究槲皮素对骨相关细胞衰老的影响,验证槲皮素通过抗骨相关细胞衰老作用对绝经后骨质疏松症的治疗作用。方法选取小鼠骨细胞样细胞MLO-Y4及成骨细胞样细胞MC3T3-E1,构建体外压力诱导的成熟前衰老(stress induced premature senescence, SIPS)模型,通过qRT-PCR法和细胞衰老相关β-半乳糖苷酶染色确定细胞衰老样变化,利用CCK-8法确定槲皮素体外工作浓度,验证槲皮素在骨相关细胞SIPS中的作用。建立去势小鼠骨质疏松模型,槲皮素灌胃给药,与经典雌激素疗法相比较,利用micro-CT扫描分析骨参数及骨微结构的变化,并通过qPCR检测小鼠皮质骨内衰老相关基因p21、p53,衰老相关分泌表型(senescence associated secretory phenotype, SASP)TNF-α、IL-6以及破骨相关基因TRAP、CTSK和成骨相关基因OCN、RUNX2的表达情况。结果体外实验证明槲皮素能有效抑制骨相关细胞SIPS样改变( P <0.05)。体内实验发现,给药12周后,相较对照组小鼠,槲皮素组小鼠股骨骨表面积与骨体积比值(BS/BV)和骨小梁分离度(***)显著降低( P <0.05),骨小梁数量(Tb.N)显著升高( P < 0.05),骨质疏松程度减轻,较雌激素疗法差异无统计学意义,并伴骨内SIPS相关基因p21、p53及SASP水平下调( P <0.05),成骨水平不受明显抑制。结论槲皮素可通过抑制细胞衰老挽救由雌激素缺乏导致的骨丢失;这可能成为绝经后骨质疏松症治疗的新手段。
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