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Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway
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/an...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898105/ https://www.ncbi.nlm.nih.gov/pubmed/35256897 http://dx.doi.org/10.1155/2022/3889318 |
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author | Cui, Mingming Liu, Jilong Geng, Li Li, Qianqian Xi, Leiming |
author_facet | Cui, Mingming Liu, Jilong Geng, Li Li, Qianqian Xi, Leiming |
author_sort | Cui, Mingming |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8898105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-88981052022-03-06 Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway Cui, Mingming Liu, Jilong Geng, Li Li, Qianqian Xi, Leiming J Healthc Eng Research Article 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. Hindawi 2022-02-26 /pmc/articles/PMC8898105/ /pubmed/35256897 http://dx.doi.org/10.1155/2022/3889318 Text en Copyright © 2022 Mingming Cui et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Cui, Mingming Liu, Jilong Geng, Li Li, Qianqian Xi, Leiming Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway |
title | Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway |
title_full | Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway |
title_fullStr | Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway |
title_full_unstemmed | Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway |
title_short | Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch–Schönlein Purpura via NF-κB Signaling Pathway |
title_sort | let-7a targeting tnfapi3 promotes vascular endothelial cell apoptosis of pediatric patients with henoch–schönlein purpura via nf-κb signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898105/ https://www.ncbi.nlm.nih.gov/pubmed/35256897 http://dx.doi.org/10.1155/2022/3889318 |
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