AUDA suppresses apoptosis of HCAECs induced by TNF and serum of Kawasaki disease patients by inhibiting endoplasmic reticulum stress

AUDA通过抑制内质网应激来抑制TNF和川崎病患者血清诱导的HCAEC细胞凋亡。

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Abstract

Kawasaki disease (KD) is an acute autoimmune vasculitis and the most common cause of acute vasculitis and acquired heart disease in children. 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) was identified as a potential therapeutic drug for KD, although its mechanism remained unclear. HCAECs were treated with TNF and serum from patients with KD to construct a KD cell model. CCK8, Elisa, and flow cytometry were performed to evaluate cell function, and western blot was used to detect target proteins. TNF and KD serum induced endoplasmic reticulum stress (ERS) and apoptosis in HCAECs. AUDA alleviated ERS and apoptosis induced by TNF or KD serum, as well as the inhibition of cell viability. Mechanistically, STAT1 transcription enhancer (2-NP) 2-NP inhibited the promoting effect of AUDA on cell proliferation and blocked the inhibitory effect of AUDA on ERS in TNF or KD serum-treated HCAECs. AUDA inhibits TNF and KD serum-induced ERS and apoptosis. This study improves our understanding of the pathogenesis of KD and provides a potential theoretical basis for its treatment.

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