PARP3 promotes macrophage inflammation via mono ADP ribosylation of Ppia Glu140 DOI Creative Commons
Rong Fan,

Rihong Zhu,

Xiujing Cao

и другие.

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Июнь 3, 2025

Acute lung injury (ALI) carries significant mortality with limited targeted therapies. Macrophages drive early inflammatory propagation in ALI, exacerbating pulmonary inflammation. While ADP-ribosylation is a dynamic and reversible post-translational modification (PTM) associated diseases, its role macrophage-mediated inflammation remains unclear. Murine ALI model was established via intratracheal instillation lipopolysaccharide (LPS). The tissues cultured mouse macrophage line (RAW264.7) treated LPS were used to assess the expression of poly ADP-ribose polymerases (Parps). RNA sequencing (RNA-seq) identified differentially expressed genes (DEGs) following Parp3 knockdown (siParp3) LPS-stimulated RAW264.7 cells, subsequent pathway analysis transcription factors (TFs) profiling gene ontology (GO) enrichment. In peptidyl-prolyl cis-trans isomerase A (Ppia) modulated by siRNA or plasmid transfection. PARP3-Ppia interaction assessed immunoprecipitation. Modification alterations due mutations at Ppia sites Enzyme-linked immune sorbent assay (ELISA) quantify secretion. evaluate lung-protective therapeutic effects PARP3 inhibitor ME0328 detecting cytokines, phosphorylation p65 histopathology. induced cells tissues, correlating elevated cytokines. 52 overlapping DEGs mainly enriched Toll-like receptor (TLR) signaling pathway. promoted NF-κB activation. blocked activation tissues. Immunoprecipitation confirmed that interacted Ppia. modified mono ADP-ribosylation. Ppia-E140 most related site. mutation E140 inhibited response, secretion vivo, reduced alleviated edema mitigated histopathological damage. We as downstream mediated for promote through Our findings provide evidence on Understanding regulation from may insight into pro-inflammatory mechanisms opportunities effective treat acute injury.

Язык: Английский

Targeting ferroptosis offers therapy choice in sepsis-associated acute lung injury DOI
Yu Wang, Weixue Wang, Yi Zhang

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 283, С. 117152 - 117152

Опубликована: Дек. 8, 2024

Язык: Английский

Процитировано

4
Development of a ferroptosis-related gene prognostic model and molecular subgroups characterization in sepsis DOI
Yajing Wang,

Zhong-Zheng Bian

Molecular Immunology, Год журнала: 2025, Номер 178, С. 1 - 11

Опубликована: Янв. 6, 2025

Язык: Английский

Процитировано

0
NAT10 induces mitochondrial dysfunction in lung epithelial cells by acetylating HMGB1 to exacerbate Pseudomonas aeruginosa-induced acute lung injury DOI

Miaoyi Huang,

Jianying Li, Jie Bai

и другие.

Microbial Pathogenesis, Год журнала: 2025, Номер unknown, С. 107364 - 107364

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Theabrownins improve burn-induced kidney injury by increasing the levels of guanidinoacetic acid and fumaric acid DOI
You Gao,

Changshun Han,

Zhiyuan Chen

и другие.

Phytomedicine, Год журнала: 2025, Номер 140, С. 156609 - 156609

Опубликована: Март 7, 2025

Язык: Английский

Процитировано

0
NAT10 Regulates LPS-Induced Inflammation via Stabilization of N4-Acetylated PTX3 mRNA in Human Dental Pulp Stem Cells DOI Open Access

Zihan Ni,

Luhui Cai,

I‐Chen Tsai

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(9), С. 4325 - 4325

Опубликована: Май 2, 2025

Severe dental pulp inflammation can lead to tissue lysis and destruction, underscoring the necessity for effective treatment of pulpitis. N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification has recently emerged as a key regulator in inflammatory processes. However, whether NAT10 affects response human stem cells (hDPSCs) remains unelucidated. In this study, elevated expression was observed pulpitis tissues LPS-stimulated hDPSCs. Knockdown led reduced gene lower reactive oxygen species (ROS) production hDPSCs, while chemotactic migration macrophages also suppressed. Similar results were when hDPSCs treated with Remodelin, an inhibitor NAT10. Differentially expressed genes identified through RNA sequencing significantly enriched signaling pathways after depletion. Among differential genes, pentraxins 3 (PTX3) potential target due presence ac4C site its known ability regulate inflammation. The mRNA protein levels PTX3 NAT10-deficient cells, along decrease stability. Exogenous supplementation partially reversed inhibition induced by knockdown. Further evidence vivo revealed that Remodelin attenuated severity rats summary, these data indicated deficiency inhibited stability further hDPSC inflammation, might be therapeutic agent capping.

Язык: Английский

Процитировано

0
PARP3 promotes macrophage inflammation via mono ADP ribosylation of Ppia Glu140 DOI Creative Commons
Rong Fan,

Rihong Zhu,

Xiujing Cao

и другие.

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Июнь 3, 2025

Acute lung injury (ALI) carries significant mortality with limited targeted therapies. Macrophages drive early inflammatory propagation in ALI, exacerbating pulmonary inflammation. While ADP-ribosylation is a dynamic and reversible post-translational modification (PTM) associated diseases, its role macrophage-mediated inflammation remains unclear. Murine ALI model was established via intratracheal instillation lipopolysaccharide (LPS). The tissues cultured mouse macrophage line (RAW264.7) treated LPS were used to assess the expression of poly ADP-ribose polymerases (Parps). RNA sequencing (RNA-seq) identified differentially expressed genes (DEGs) following Parp3 knockdown (siParp3) LPS-stimulated RAW264.7 cells, subsequent pathway analysis transcription factors (TFs) profiling gene ontology (GO) enrichment. In peptidyl-prolyl cis-trans isomerase A (Ppia) modulated by siRNA or plasmid transfection. PARP3-Ppia interaction assessed immunoprecipitation. Modification alterations due mutations at Ppia sites Enzyme-linked immune sorbent assay (ELISA) quantify secretion. evaluate lung-protective therapeutic effects PARP3 inhibitor ME0328 detecting cytokines, phosphorylation p65 histopathology. induced cells tissues, correlating elevated cytokines. 52 overlapping DEGs mainly enriched Toll-like receptor (TLR) signaling pathway. promoted NF-κB activation. blocked activation tissues. Immunoprecipitation confirmed that interacted Ppia. modified mono ADP-ribosylation. Ppia-E140 most related site. mutation E140 inhibited response, secretion vivo, reduced alleviated edema mitigated histopathological damage. We as downstream mediated for promote through Our findings provide evidence on Understanding regulation from may insight into pro-inflammatory mechanisms opportunities effective treat acute injury.

Язык: Английский

Процитировано

0