Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis.
Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis.
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DOI：
10.1042/bsr20160336
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发表时间：
2016-12
影响因子：
4
通讯作者：
Mulay SR
中科院分区：
文献类型：
--
作者：
Honarpisheh M;Desai J;Marschner JA;Weidenbusch M;Lech M;Vielhauer V;Anders HJ;Mulay SR
调节性坏死（RN）相关分子的物种特异性和器官特异性表达尚不清楚。我们测定了肿瘤坏死因子受体1（TNFR 1）、受体活化蛋白激酶（RIPK）1、RIPK 3、混合谱系激酶结构域样（MLKL）、CASP 8、Fas相关蛋白与死亡结构域（FADD）、细胞凋亡抑制蛋白（CIAP）1、CIAP 2、谷胱甘肽过氧化物酶4（GPX 4）、亲环素D（CYPD）、CASP 1、人和小鼠实体器官中的NLRP 3和聚（ADP-核糖）聚合酶-1（PARP 1）。我们观察到这些分子在人类和小鼠之间的表达存在显着差异。此外，我们使用急性和慢性肾损伤模型表征了它们在急性以及持续性组织损伤和慢性组织重塑中的表达谱。我们观察到RN相关分子的诱导程度和模式高度依赖于触发和疾病发病机制。此外，我们研究了它们在狼疮样系统性自身免疫小鼠中的表达模式，结果显示MLKL、GPX 4和PARP 1在脾脏中的表达沿着疾病进展而显著增加，CASP 1、RIPK 1、RIPK 3和CYPD在早期阶段较高，但在后期阶段显著降低。相反，在肾脏中，参与焦亡的基因，例如NLRP 3和CASP 1的表达随着狼疮性肾炎（LN）的进展而显著增加，TNFR 1、RIPK 1、RIPK 3、CIAP 1/2和GPX 4的表达沿着显著降低。因此，在设计实验、解释结果以及将结论从一个物种或器官分别外推到另一个物种或器官时，应考虑RN相关分子的器官特异性和物种特异性表达。
The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, CIAP2, glutathione peroxidase-4 (GPX4), cyclophilin D (CYPD), CASP1, NLRP3 and poly(ADP-ribose) polymerase-1 (PARP1) in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice. In addition, we characterized their expression profiles in acute as well as persistent tissue injury and chronic tissue remodelling using acute and chronic kidney injury models. We observed that the degree and pattern of induction of RN-related molecules were highly dependent on the trigger and disease pathogenesis. Furthermore, we studied their expression patterns in mice with lupus-like systemic autoimmunity, which revealed that the expression of MLKL, GPX4 and PARP1 significantly increased in the spleen along disease progression and CASP1, RIPK1, RIPK3 and CYPD were higher at the earlier stages but were significantly decreased in the later stages. In contrast, in the kidney, the expression of genes involved in pyroptosis, e.g. NLRP3 and CASP1 were significantly increased and TNFR1, RIPK1, RIPK3, CIAP1/2 and GPX4 were significantly decreased along the progression of lupus nephritis (LN). Thus, the organ- and species-specific expression of RN-related molecules should be considered during designing experiments, interpreting the results as well as extrapolating the conclusions from one species or organ to another species or organ respectively.