The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of TNFR1, RIPK1, RIPK3, MLKL, CASP8, FADD, CIAP1, CIAP2, GPX4, CYPD, CASP1, NLRP3, and 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 remodeling 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 stage but was 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. 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.
- Cell death
- tissue remodeling
- ©2016 The Author(s)
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