USP7 promotes endothelial activation to aggravate sepsis-induced acute lung injury through PDK1/AKT/NF-κB signaling pathway DOI Creative Commons
Zhiyi Liu,

Xiaoyun Shi,

Tiantian Ke

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 17, 2025

Abstract Disruption of the endothelial cell barrier and subsequent inflammatory response represent a central pathological feature acute lung injury (ALI). Ubiquitination plays pivotal role in regulating protein stability, intracellular transport, enzyme activity, which is typically reversed by deubiquitinating enzymes. Nevertheless, function enzymes biology ALI remains largely uninvestigated. The present study demonstrates that expression USP7 increased instances inflammation ALI. knockdown or inhibition using specific inhibitors was observed to significantly reduce TNF-α-induced cells their adhesion capacity monocytes. Conversely, overexpression promote cells. were found be effective mitigating induced LPS. From mechanistic perspective, our findings indicate binds deubiquitinates PDK1, thereby stabilizing PDK1 promoting activity pathway In conclusion, demonstrate novel USP7-PDK1 signaling axis vascular reveal deubiquitylating PDK1. These observations suggest targeting may offer promising therapeutic strategy for treatment injury.

Language: Английский

USP7 promotes endothelial activation to aggravate sepsis-induced acute lung injury through PDK1/AKT/NF-κB signaling pathway DOI Creative Commons
Zhiyi Liu,

Xiaoyun Shi,

Tiantian Ke

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 17, 2025

Abstract Disruption of the endothelial cell barrier and subsequent inflammatory response represent a central pathological feature acute lung injury (ALI). Ubiquitination plays pivotal role in regulating protein stability, intracellular transport, enzyme activity, which is typically reversed by deubiquitinating enzymes. Nevertheless, function enzymes biology ALI remains largely uninvestigated. The present study demonstrates that expression USP7 increased instances inflammation ALI. knockdown or inhibition using specific inhibitors was observed to significantly reduce TNF-α-induced cells their adhesion capacity monocytes. Conversely, overexpression promote cells. were found be effective mitigating induced LPS. From mechanistic perspective, our findings indicate binds deubiquitinates PDK1, thereby stabilizing PDK1 promoting activity pathway In conclusion, demonstrate novel USP7-PDK1 signaling axis vascular reveal deubiquitylating PDK1. These observations suggest targeting may offer promising therapeutic strategy for treatment injury.

Language: Английский

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