Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway. (26th February 2022)

• Record Type: Journal Article
• Authors: Cui, Mingming; Liu, Jilong; Geng, Li; Li, Qianqian; Xi, Leiming
• Other Names: Rajakani Kalidoss Academic Editor.
• Is Part Of: Journal of healthcare engineering. Volume 2022(2022)
• Publication Date: 2022-02-26
• Subjects: Hospital buildings -- Environmental engineering -- Periodicals; Medical technology -- Periodicals; Medical informatics -- Periodicals; 610.28
• DOI: 10.1155/2022/3889318
• Languages: English
• ISSNs: 2040-2295

Abstract

Abstract : Objective . We aimed at exploring the role of let-7a in the pathogenesis of pediatric Henoch–Schönlein purpura (HSP) and its related mechanism. Methods . Fifty-five pediatric HSP patients and 20 paired healthy controls were included. The expressions of let-7a and TNFAIP3 were detected by RT-qPCR or/and western blot. Vessel fibrinoid necrosis was evaluated in skin tissues by PTAH staining. The serum IgA level was measured by ELISA. Cells were transfected with let-7a inhibitor and/or TNFAIP3 siRNA, accompanied by pretreatment with NF- κ B inhibitor PDTC or not. After being cultured in HSP serum, the changes in cell viability, cell apoptosis, apoptosis-related proteins, and NF- κ B pathway-related proteins were detected by CCK8, flow cytometry, and western blot. Results . The let-7a expression level was positively correlated with the serum IgA level and severity degree of vascular fibrinoid necrosis in HSP patients. Let-7a expression was significantly increased, whereas cell viability and TNFAIP3 expression were obviously decreased 48 h after HUVECs were incubated with HSP serum. Let-7a knockdown upregulated the cell viability, whereas it reduced the apoptotic ratio, apoptosis protein expressions (Bax/Bcl2 ratio, cleaved-caspase 3), and NF- κ B pathway activation (reflected by reduced P65 nuclear translocation and p-I κ B α expression) in HUVECs (all p < 0.05 ). The changes induced by let-7a knockdown were obviously reversed by TNFAIP3 siRNA transfection p < 0.05 . Besides, PDTC treatment remarkably diminished the anti-apoptosis effect of let-7a knockdown and pro-apoptosis effect of TNFAIP3 siRNA on HUVECs induced by HSP serum. Conclusions . Let-7a knockdown significantly suppressed vascular endothelial cell apoptosis induced by HSP serum by targeting TNFAPI3 via NF- κ B signaling pathway. Our findings provided a potential therapeutic target for the treatment of HSP.