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Triamcinolone Acetonide Alleviates Benign Biliary Stricture By Ameliorating Biliary Fibrosis And Inflammation
Seyeon Joo 1,2,# (Graduate Student), See Young Lee3,# (Professor), Su Yeon Lee3 (Research worker), Yeseong Hwang 1,2 (Graduate Student), Minki Kim 1,2 (Graduate Student), Jae Woong Jeong 4 (Graduate Student), Sung Ill Jang 3 (Professor), Sungsoon Fang 1,2,* (Professor)
1Graduate school of Medical Science, Brain Korea 21 Project and 2Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Korea,
3Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea,
4Department of Medicine, Yonsei University College of Medicine, Seoul, Korea
Abstract
We conducted a comprehensive series of molecular biological studies aimed at unraveling the intricate mechanisms underlying the anti-fibrotic effects of triamcinolone acetonide (TA) when utilized in conjunction with fully covered self-expandable metal stents (FCSEMS) as a therapeutic approach for the management of benign biliary strictures (BBS). To decipher the molecular mechanisms responsible for the anti-fibrotic effects of corticosteroids on gallbladder mucosa, we conducted a comprehensive analysis. This analysis included various methodologies such as immunohistochemistry, ELISA, real-time PCR, and transcriptome analysis, enabling us to examine alterations in factors related to fibrosis and inflammation at both the protein and RNA levels.
Overall, our findings revealed a dose-dependent decrease in fibrosis-related signaling with higher TA concentrations. The 15mg of steroid treatment (1X) exhibited anti-fibrosis and anti-inflammatory effects after 4 weeks, whereas the 30mg of steroid treatment (2X) rapidly reduced fibrosis and inflammation within 2 weeks in BBS. Transcriptomic analysis results consistently demonstrated significant downregulation of fibrosis- and inflammation-related pathways and genes in steroid-treated fibroblasts. The utilization of corticosteroid, specifically TA, on FCSEMS has demonstrated effective treatment for BBS, ameliorating fibrosis and inflammation. Our molecular biological analysis supports the potential development of steroid-eluted FCSEMS into a future therapeutic option for addressing BBS in humans resulting from various surgical procedures.
Abstract, Accepted Manuscript [Submitted on December 6, 2023, Accepted on January 25, 2024]
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