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.