上睑下垂
程序性细胞死亡
线粒体
生物
细胞凋亡
细胞生物学
半胱氨酸蛋白酶3
萎缩
病理
医学
生物化学
遗传学
作者
Meirong Liu,Ling Li,Tingjun Dai,Ying Hou,Wei Li,Yuying Zhao,Qi Fang,Chuanzhu Yan
摘要
Abstract Different mechanisms have been proposed to explain the pathological basis of perifascicular atrophy (PFA), a pathognomonic histologic feature of dermatomyositis (DM); however, the detailed mechanisms remain to be elucidated. There is mitochondrial dysfunction in PFA and expression of mitochondrial apoptosis molecules has been reported in DM. Overexpression of gasdermin E (GSDME) can turn mitochondrial apoptosis to mitochondrial pyroptosis, a newly characterized form of programmed cell death. We determined the expression of proteins involved in the caspase-3- and GSDME-dependent mitochondrial pyroptotic pathway, including BAX, BAK, cytochrome C, caspase-9, caspase-3, GSDME, and IL-1α, in biopsied muscles from DM and control patients. Immunohistochemical analysis showed that those markers were expressed in most fibers in PFA in DM. GSDME-positive and IL-1α-positive staining was mainly localized around punched-out vacuoles or sarcolemma. These markers were significantly upregulated at the protein and mRNA levels in DM versus controls. Our results suggest that caspase-3- and GSDME-dependent mitochondrial pyroptosis are involved in the pathogenetic mechanisms of PFA in DM and that targeting GSDME-dependent mitochondrial pyroptosis may be an effective therapeutic approach for this condition.
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