LMNA-related muscular dystrophies are caused by mutations of the LMNA gene. Inflammatory changes and cellular apoptosis are significant pathological findings in the muscle cells of these patients. We aimed to investigate the roles of nuclear factor-κB (NF-κB) mediated inflammation as a molecular mechanism for the pathogenesis of LMNA-related muscular dystrophies. Muscle specimen of a patient with LMNA gene mutation (c.1117A>G, p.I373V, reported in our previous work) showed significant inflammatory changes. The ultrastructure of muscle cells showed severe nuclear abnormalities compared with the control. Therefore, we used this mutation to establish mutant cell line for in vitro studies. Transfected human embryonic kidney 293 (HEK293) cells containing a mutant construct from this patient showed irregular nuclear morphology. Mass spectrometry analysis suggested genomic instability and augmented expression of apoptosis-related genes. We detected activation of NF-κB pathway in LMNA mutant cells which promoted the expression of downstream inflammatory factors. The LMNA mutation also activated the molecular pathway of apoptosis in LMNA mutant cells. These are important molecular mechanisms underlying the pathogenesis of LMNA-related muscular dystrophies. Our research provides crucial evidence for future pathogenetic studies and possible treatment strategies for LMNA-related muscular dystrophies.

LMNA相关的肌营养不良是由LMNA基因的突变引起的。在这些患者的肌肉细胞中，炎症变化和细胞凋亡是重要的病理发现。我们旨在研究核因子-κB（NF-κB）介导的炎症作为LMNA相关性肌营养不良症发病机理的分子机制的作用。LMNA患者的肌肉样本基因突变（c.1117A> G，p.I373V，在我们先前的研究中报道）显示出明显的炎症变化。与对照组相比，肌肉细胞的超微结构显示出严重的核异常。因此，我们使用该突变建立了用于体外研究的突变细胞系。包含来自该患者的突变体构建体的转染的人类胚胎肾293（HEK293）细胞显示出不规则的核形态。质谱分析表明基因组不稳定性和凋亡相关基因的表达增加。我们检测到LMNA突变细胞中NF-κB通路的激活，这促进了下游炎症因子的表达。该LMNA基因突变也被激活细胞凋亡的分子途径LMNA突变细胞。这些是与LMNA相关的肌肉营养不良的发病机理的重要分子机制。我们的研究为LMNA相关的肌营养不良症的未来病原学研究和可能的治疗策略提供了重要的证据。