The role of apolipoprotein C1 in mediating pyroptosis in Hashimoto's thyroiditis via TLR10/MyD88/NF-κB pathway

Inflammation is an important pathogenic factor that leads to thyroid follicular epithelial cells injury after Hashimoto's thyroiditis (HT). Recent studies proposed relationships between pyroptosis and apolipoproteins in HT. However, the molecular signatures involved in the pathophysiological changes that occur during the course of HT remain ambiguous.

The current study obtained thyroid tissues from HT patients and investigated the genes and pathways involved in HT by transcriptome sequencing analysis. Besides, ELISA, immunohistochemical staining, western blot analysis, LDH release assay and RNA interference were conducted to validate the expression levels of dysregulated proteins and underlying pathways.

Transcriptomic analysis demonstrated that HT was associated with the enrichment of genes related to the inflammatory response, pyroptosis, and regulation of the lipid metabolic process. The transcription level of APOC1 gene ranked highest among apolipoproteins, and genes associated with the interleukin (IL)-18 signaling pathway and the NLRP3 inflammasome were upregulated. The expression levels of IL-18, NLRP3, and APOC1 proteins were increased in HT patients. Furthermore, in vitro studies using LPS-treated Nthy-ori 3-1 thyroid cells confirmed that APOC1 induced pyroptosis through TLR10/MyD88/NF-κB p65 dependent pathway.

APOC1 probably participated in the pathogenesis of HT by mediating TFCs pyroptosis through TLR10/MyD88/NF-κB pathway.