Escin, a natural triterpene saponin mixture obtained from the horse chestnut tree (Aesculus hippocastanum), has been used for the treatment of chronic venous insufficiency (CVI), hemorrhoids, and edema. However, it is unclear how escin protects against endothelial barrier dysfunction induced by pro-inflammatory high mobility group protein 1 (HMGB1). Here, we report that escin can suppress (a) HMGB1-induced overexpression of the aquaporin-1 (AQP1) water channel in endothelial cells and (b) HMGB1-induced increases in endothelial cell permeability. This is the first report that escin inhibits AQP1 and alleviates barrier dysfunction in HMGB1-induced inflammatory response.
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http://dx.doi.org/10.1002/2211-5463.12622 | DOI Listing |
Int J Mol Sci
June 2024
Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan.
Abnormalities in mucosal immunity are involved in the onset and progression of ulcerative colitis (UC), resulting in a high incidence of colorectal cancer (CRC). While high-mobility group box-1 (HMGB1) is overexpressed during colorectal carcinogenesis, its role in UC-related carcinogenesis remains unclear. In the present study, we investigated the role of HMGB1 in UC-related carcinogenesis and sporadic CRC.
View Article and Find Full Text PDFJ Am Chem Soc
July 2024
State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, and Department of Chemical Biology at School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
The receptor for advanced glycation end products (RAGE) plays a crucial role in inflammation-related pathways and various chronic diseases. Despite the recognized significance of N-glycosylation in the ligand-binding V domain (VD) of RAGE, a comprehensive understanding of the site-activity and structure-activity relationships is lacking due to the challenges in obtaining homogeneous glycoprotein samples through biological expression. Here, we combined chemical and chemoenzymatic approaches to synthesize RAGE-VD and its congeners with Asn3-glycosylation by incorporating precise N-glycan structures.
View Article and Find Full Text PDFFront Immunol
December 2023
Guangdong-Hong Kong Joint Laboratory for Immunological and Genetic Kidney Disease, Departments of Nephrology and Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
"Cytokine storm" is common in critically ill COVID-19 patients, however, mechanisms remain largely unknown. Here, we reported that overexpression of SARS-CoV-2 N protein in diabetic db/db mice significantly increased tubular death and the release of HMGB1, one of the damage-associated molecular patterns (DAMPs), to trigger M1 proinflammatory macrophage activation and production of IL-6, TNF-α, and MCP-1 via a Mincle-Syk/NF-κB-dependent mechanism. This was further confirmed that overexpression of SARS-CoV-2 N protein caused the release of HMGB1 from injured tubular cells under high AGE conditions, which resulted in M1 macrophage activation and production of proinflammatory cytokines via a Mincle-Syk/NF-κB-dependent mechanism.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2024
Department of Cardiology, He Xian Memorial Affiliated Hospital of Southern Medical University, Guangzhou, China.
Oxidized low-density lipoprotein (ox-LDL) mediated inflammatory damage, which possibly induces atherosclerosis (AS); however, the role of miRNA in this process has rarely been reported. In this paper, we study the ox-LDL-related endothelial cell damage and changes of macrophages. The bioinformatics method was used to analyze the expression changes of miRNA in AS patients, luciferase assay was used to study the interaction of protein and miRNA, and co-IP and ubiquitination experiments were used to analyze protein interaction.
View Article and Find Full Text PDFTheranostics
August 2023
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Metastasis is a major cause of HCC-related deaths with no effective pharmacotherapies. Chronic inflammation promotes HCC dissemination, however, its underlying mechanisms are not fully understood. Here, we investigated the role of Krüppel-like factor 7 (KLF7) in inflammation-provoked HCC metastasis and proposed therapeutic strategies for KLF7-positive patients.
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