NRIP1 aggravates lung injury caused by Pseudomonas aeruginosa in mice by increasing PIAS1 ubiquitination.
Aging (Albany NY)
; 14(8): 3529-3539, 2022 04 23.
Article
em En
| MEDLINE
| ID: mdl-35460552
ABSTRACT
Recently, evidence has shown that nuclear receptor interacting protein 1 (NRIP1) is involved in acute lung injury (ALI) progression, but the specific mechanism remains unclear. Pseudomonas aeruginosa (PA)-treated TC-1 cells were transfected with pcDNA-NRIP1 or si-NRIP1, and we found that overexpression of NRIP1 inhibited cell viability and promoted cell apoptosis and secretion of inflammatory factors, and transfection of si-NRIP1 reversed these effects. Furthermore, online bioinformatics analysis and co-immunoprecipitation assay results indicated that NRIP1 could bind to Ubiquitin Conjugating Enzyme E2I (UBE2I), and promoted UBE2I expression. Next, the PA-treated TC-1 cells were transfected with si-NRIP1 alone or together with pcDNA-UBE2I, and we observed that transfection with si-NRIP1 inhibited UBE2I expression, promoted cell viability, and reduced cell apoptosis and inflammatory factor secretion, which could be reversed by UBE2I overexpression. Moreover, UBE2I could bind to protein inhibitor of activated signal transducer and activators of transcription 1 (PIAS1). Overexpression of NRIP1 promoted UBE2I expression and inhibited PIAS1 expression, and NRIP1 promoted PIAS1 ubiquitination and degradation by UBE2I. The PA-treated TC-1 cells were transfected with si-UBE2I alone or together with si-PIAS1, and the results indicated that transfection of si-UBE2I had the same effect as transfection of si-NRIP1. Finally, our in vivo findings indicated that the expression of NRIP1 and UBE2I was decreased, and PIAS1 expression was increased, in the lung tissues of mice with NRIP1 knocked-down, and the inflammatory infiltration in the lung tissue was reduced. In conclusion, our study demonstrates that NRIP1 aggravates PA-induced lung injury in mice by promoting PIAS1 ubiquitination.
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MEDLINE
Assunto principal:
Proteínas Inibidoras de STAT Ativados
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Lesão Pulmonar Aguda
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article