Pentraxin-3 modulates hepatocyte ferroptosis and the innate immune response in LPS-induced liver injury DOI Creative Commons
H Wang,

Zhaojie Su,

Yunyun Qian

et al.

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Dec. 12, 2024

Abstract The liver plays a crucial role in the immune response during endotoxemia and is one of critical targets for sepsis-related injuries. As secretory factor involved inflammation, pentraxin-3 (PTX3) has been demonstrated to regulate hepatic homeostasis; however, relationship between PTX3 cell crosstalk cells hepatocytes remains incompletely understood. In this study, we revealed that, compared with WT mice, Ptx3 −/− mice lipopolysaccharide (LPS)-induced exhibited alleviated damage, reduced serum alanine transaminase aspartate levels an improved survival rate. Mechanistically, RNA-Seq western blot results that knockdown increased expression Tfrc Ccl20 ; consequently, deficiency regulated LPS-induced hepatocyte ferroptosis via mitochondrial reactive oxygen species Fe 2+ recruited more macrophages by CCL20/CCR6 axis be inflammation clearance harmful substances. Moreover, immunofluorescence staining confirmed NF-κB signaling pathway was upregulated upon LPS treatment -knockdown macrophages, promoting phagocytosis polarization toward M1 macrophages. Collectively, our findings show absence can ameliorate sepsis-induced injury regulating promote recruitment These offer key basis development effective treatments acute infections.

Language: Английский

CircLDLRAD3 inhibits Oral squamous cell carcinoma progression by regulating miR‐558/Smad4/TGF‐β DOI Creative Commons
Xue Zhang, Guang‐Yu Guo,

Ru‐Yue Liu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 27(21), P. 3271 - 3285

Published: Aug. 10, 2023

Abstract Oral squamous cell carcinoma (OSCC) is a malignant neoplasm with high mortality and morbidity. The role of circRNA its molecular mechanism in OSCC remains largely unknown. study aims to explore the novel circular RNA (circLDLRAD3) underlying mechanism. PCR fluorescence situ hybridization were used expression features circLDLRAD3 OSCC. effects on behaviour investigated using CCK‐8, colony formation assay, transwell animal experiments. Bioinformatics analysis along dual luciferase reporter assay RIP reveal interaction between circLDLRAD3, miR‐558 Smad4. It was revealed that exhibited low status CircLDLRAD3 inhibits proliferation, migration, invasion cells both vitro vivo. Mechanistically, could bind positively regulate target gene Smad4 expression. Rescue experiments further confirmed overexpression knockdown reverse influence phenotypes. Moreover, TGF‐β signalling pathways EMT through miR‐558/Smad4 axis. Our found downregulated verified tumour suppressor function sponging miR‐558/Smad4/TGF‐β characterization such regulating network uncovers an important progression, which provide promising targets targeted therapy strategies for future.

Language: Английский

Citations

2
Smad4 Loss in the Mouse Intestinal Epithelium Alleviates the Pathological Fibrotic Response to Injury in the Colon DOI Open Access

Zahra Hashemi,

Thompson Hui,

Alexander T.H. Wu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 12, 2024

ABSTRACT Mucosal healing is associated with better clinical outcomes in patients inflammatory bowel diseases (IBDs). Unresolved injury and inflammation, on the other hand, increases pathological fibrosis predisposition to cancer. Loss of Smad4, a tumor suppressor, known increase colitis-associated cancer mouse models chronic IBD. Since common biological processes are involved both repair growth, we sought investigate effect Smad4 loss response epithelial injury. To this end, was knocked out specifically intestinal epithelium transcriptomic morphological changes compared between wild type mice knock after DSS-induced We find that alleviates enhances mucosal repair. The specific indicate molecular affect extracellular matrix (ECM) promote enhanced These findings suggest wound alleviate fibrotic DSS. Therefore, these could be exploited develop therapies normal prevent fibrosis. NEW AND NOTEWORTHY show due colonic DSS an IBD model acute inflammation. Most notably, collagen deposition ECM, as opposed lamina propria, correlates enhance healing. This first report providing alleviated DSS-IBD vivo .

Language: Английский

Citations

0
Activation of the Α7nachr by Gts-21 Mitigates Septic Tubular Cell Injury and Modulates Macrophage Infiltration DOI
Aobing Yang, Chia-Hsien Wu,

S. Matsuo

et al.

Published: Jan. 1, 2024

Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI

Language: Английский

Citations

0
Epithelial-specific loss of Smad4 alleviates the fibrotic response in an acute colitis mouse model DOI Creative Commons

Zahra Hashemi,

Thompson Hui,

Alex Wu

et al.

Life Science Alliance, Journal Year: 2024, Volume and Issue: 7(12), P. e202402935 - e202402935

Published: Oct. 4, 2024

Mucosal healing is associated with better clinical outcomes in patients inflammatory bowel disease. But the epithelial-specific contribution to mucosal vivo poorly understood. We evaluated an acute dextran sulfate sodium mouse model that shows alleviated colitis response after loss of Smad4. find enhanced epithelial wound alleviates fibrotic response. Dextran caused increased mesenchymal collagen deposition—indicative fibrosis—within a week WT but not Smad4 KO colon. The correlated decreased proliferation WT, whereas uninterrupted and expanded zone were observed colon epithelium. Furthermore, showed extracellular matrix alterations promote regeneration. Our data suggest epithelium key determinant vivo, implicating as strategy against fibrosis disease patients.

Language: Английский

Citations

0
Pentraxin-3 modulates hepatocyte ferroptosis and the innate immune response in LPS-induced liver injury DOI Creative Commons
H Wang,

Zhaojie Su,

Yunyun Qian

et al.

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Dec. 12, 2024

Abstract The liver plays a crucial role in the immune response during endotoxemia and is one of critical targets for sepsis-related injuries. As secretory factor involved inflammation, pentraxin-3 (PTX3) has been demonstrated to regulate hepatic homeostasis; however, relationship between PTX3 cell crosstalk cells hepatocytes remains incompletely understood. In this study, we revealed that, compared with WT mice, Ptx3 −/− mice lipopolysaccharide (LPS)-induced exhibited alleviated damage, reduced serum alanine transaminase aspartate levels an improved survival rate. Mechanistically, RNA-Seq western blot results that knockdown increased expression Tfrc Ccl20 ; consequently, deficiency regulated LPS-induced hepatocyte ferroptosis via mitochondrial reactive oxygen species Fe 2+ recruited more macrophages by CCL20/CCR6 axis be inflammation clearance harmful substances. Moreover, immunofluorescence staining confirmed NF-κB signaling pathway was upregulated upon LPS treatment -knockdown macrophages, promoting phagocytosis polarization toward M1 macrophages. Collectively, our findings show absence can ameliorate sepsis-induced injury regulating promote recruitment These offer key basis development effective treatments acute infections.

Language: Английский

Citations

0