Tissue & cell · 2025
OTUD5 enhances activation of multiple cell death pathways and hyperoxia-induced lung injury by stabilizing TRAF4 and activating the p38/JNK pathway.
СтатьяНазвание и аннотация: Перевод в очереди
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Gu Xia, Zhu Tong, Hang Guihua, Chen Wenjie, Chen Huiping
Аннотация
OBJECTIVE: This study aims to elucidate the role of OTUD5 in hyperoxia-induced lung injury and to explore its potential as a therapeutic target for mitigating oxidative stress-related lung damage.
METHODS: AAV9-OTUD5 siRNA was administered via intratracheal injection in a mouse model to silence OTUD5 before exposure to 60 % O2 for 24 h. Lung tissues were analyzed using histological techniques (HE, Masson's, PAS staining) and quantified for collagen deposition and airway epithelial changes. Additionally, qPCR and WB analysisWB analysis assessed OTUD5 and TRAF4 expression levels. Co-immunoprecipitation and dual-immunofluorescence assays evaluated the interaction between OTUD5 and TRAF4. Apoptosis was measured via TUNEL staining and Cleaved-Caspase-3 expression analysis, while ROS levels were assessed using MitoSOX.
RESULTS: Silencing OTUD5 significantly reduced lung injury, evidenced by improved histological architecture and decreased collagen deposition. OTUD5 knockdown attenuated apoptosis markers and ROS production in BEAS-2B cells exposed to hyperoxia. Co-IP assays confirmed that OTUD5 stabilizes TRAF4, linking it to the activation of the p38/JNK signaling pathway. Furthermore, treatment with metformin and berberine chloride diminished the protective effects of OTUD5 knockdown in vivo.
CONCLUSION: OTUD5 plays a critical role in hyperoxia-induced lung injury through the regulation of TRAF4 stability and apoptotic pathways. Targeting OTUD5 may provide a novel therapeutic strategy to mitigate lung damage in conditions characterized by oxidative stress.
METHODS: AAV9-OTUD5 siRNA was administered via intratracheal injection in a mouse model to silence OTUD5 before exposure to 60 % O2 for 24 h. Lung tissues were analyzed using histological techniques (HE, Masson's, PAS staining) and quantified for collagen deposition and airway epithelial changes. Additionally, qPCR and WB analysisWB analysis assessed OTUD5 and TRAF4 expression levels. Co-immunoprecipitation and dual-immunofluorescence assays evaluated the interaction between OTUD5 and TRAF4. Apoptosis was measured via TUNEL staining and Cleaved-Caspase-3 expression analysis, while ROS levels were assessed using MitoSOX.
RESULTS: Silencing OTUD5 significantly reduced lung injury, evidenced by improved histological architecture and decreased collagen deposition. OTUD5 knockdown attenuated apoptosis markers and ROS production in BEAS-2B cells exposed to hyperoxia. Co-IP assays confirmed that OTUD5 stabilizes TRAF4, linking it to the activation of the p38/JNK signaling pathway. Furthermore, treatment with metformin and berberine chloride diminished the protective effects of OTUD5 knockdown in vivo.
CONCLUSION: OTUD5 plays a critical role in hyperoxia-induced lung injury through the regulation of TRAF4 stability and apoptotic pathways. Targeting OTUD5 may provide a novel therapeutic strategy to mitigate lung damage in conditions characterized by oxidative stress.