LncRNA H19 aggravates primary graft dysfunction after lung transplantation via KLF5-mediated activation of CCL28.
Am J Transplant
; 23(10): 1536-1550, 2023 10.
Article
en En
| MEDLINE
| ID: mdl-37394140
ABSTRACT
The present study aims to elucidate the possible involvement of H19 in primary graft dysfunction (PGD) following lung transplantation (LT) and the underlying mechanism. The transcriptome data were obtained through high-throughput sequencing analysis, and the differential long noncoding RNAs and messenger RNAs were screened for coexpression analysis. The interaction among H19, KLF5 and CCL28 was analyzed. A hypoxia-induced human pulmonary microvascular endothelial cell injury model was established, in which H19 was knocked down to elucidate its effect on the lung function, inflammatory response, and cell apoptosis. An orthotopic left LT model was constructed for in vivo mechanistic validation. High-throughput transcriptome sequencing analysis revealed the involvement of the H19/KLF5/CCL28 signaling axis in PGD. Silencing of H19 reduced inflammatory response and thus improved PGD. CCL28 secreted by human pulmonary microvascular endothelial cells after LT recruited neutrophils and macrophages. Mechanistic investigations indicated that H19 augmented the expression of CCL28 by binding to the transcription factor KLF5. Abundant expression of CCL28 reversed the alleviating effect of H19 silencing on PGD. In conclusion, the results point out that H19 exerts a promoting effect on PGD through increasing KLF5 expression and the subsequent CCL28 expression. Our study provides a novel insight into the mechanism of action of H19.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trasplante de Pulmón
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MicroARNs
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Disfunción Primaria del Injerto
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ARN Largo no Codificante
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2023
Tipo del documento:
Article