Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway

Author:

Cui Mingming1,Liu Jilong2,Geng Li3,Li Qianqian4,Xi Leiming5ORCID

Affiliation:

1. First Clinical College, Shandong University of Traditional Chinese Medicine, No. 4655, Daxue Road, University Science Park, Changqing District, Jinan, Shandong 250355, China

2. Department of Pediatrics, Cao County People’s Hospital, Qinghe Road East, Fumin Avenue South, Caoxian Development District, Heze, Shandong 274400, China

3. Department of Physiotherapy, Jinan City People’s Hospital, No. 001, Xuehu Street, Laiwu District, Jinan, Shandong 271199, China

4. Department of Second Internal Medicine, Jinan Shizhong People’s Hospital, No. 61, Langmaoshan Road, Jinan, Shandong 250002, China

5. Department of Pediatrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 42, Wenhuaxi Road, Jinan, Shandong 250011, China

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-κB inhibitor PDTC or not. After being cultured in HSP serum, the changes in cell viability, cell apoptosis, apoptosis-related proteins, and NF-κB 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-κB pathway activation (reflected by reduced P65 nuclear translocation and p-IκBα 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-κB signaling pathway. Our findings provided a potential therapeutic target for the treatment of HSP.

Publisher

Hindawi Limited

Subject

Health Informatics,Biomedical Engineering,Surgery,Biotechnology

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