Recombinant soluble thrombomodulin attenuates cisplatin-induced intestinal injury by inhibiting intestinal epithelial cell-derived cytokine secretion.

Autor: Yamaguchi T; Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.; Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan., Gaowa A; Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan. arong-g@doc.medic.mie-u.ac.jp., Park EJ; Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan., Tawara I; Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan., Shimaoka M; Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2023 Oct; Vol. 50 (10), pp. 8459-8467. Date of Electronic Publication: 2023 Aug 26.
DOI: 10.1007/s11033-023-08762-1
Abstrakt: Background: Intestinal injury is one of the main side-effects of cisplatin chemotherapy, impairing the quality of life in patients with cancer. In this study, we investigated the protective effects of recombinant soluble thrombomodulin (rsTM), which is a potent anti-inflammatory agent, on cisplatin-induced intestinal injury.
Methods: We first evaluated the effects of rsTM on intestinal injury caused by cisplatin in mice in vivo. Disease progression was monitored by analyzing loss of body weight and histological changes in intestinal tissue. We then investigated the effects of rsTM on mouse intestinal organoid formation and growth in vitro. Gene expression levels were analyzed by quantitative real-time polymerase chain reaction and Western blotting.
Results: rsTM treatment significantly attenuated the loss of body weight, histological damage and gene expression levels of pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α and high-mobility group box-1 in a cisplatin-treated mouse model. Furthermore, rsTM alleviated the inflammatory response and apoptosis in a cisplatin-treated intestinal epithelial organoid model.
Conclusion: rsTM suppresses cisplatin-induced intestinal epithelial cell-derived cytokine production and alleviates intestinal mucositis.
(© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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