Astilbin Alleviates Radiation-Induced Pulmonary Fibrosis via circPRKCE Targeting the TGF-β/Smad7 Pathway to Inhibit Epithelial–Mesenchymal Transition

<b>Purpose:</b> This study aimed to clarify the protective effect of astilbin (AST) on radiation-induced pulmonary fibrosis (RIPF) and explore its underlying molecular mechanism, focusing on non-coding RNAs. <b>Methods:</b> Mouse lung epithelial cells (MLE-12 and TC-1) and C57BL/6J mice were used to establish in vitro radiation injury models and in vivo RIPF models, respectively. Cell viability, apoptosis, the epithelial-to-mesenchymal transition (EMT), and fibrosis-related markers were assessed using cell-counting kit-8 assays, Western blotting, immunohistochemistry, and histological staining. High-throughput sequencing identified differentially expressed circRNAs. The mechanistic studies included RNA-FISH, a dual-luciferase reporter assay, an RNA immunoprecipitation (RIP) assay, and loss-of-function experiments. <b>Results:</b> AST significantly alleviated radiation-induced apoptosis and EMT in vitro, as well as RIPF in vivo. AST treatment reduced collagen deposition, fibrosis-related protein expression, and EMT marker changes. High-throughput sequencing revealed that AST upregulated <i>circPRKCE</i>, a non-coding RNA that functions through a ceRNA mechanism by binding to miR-15b-5p, thereby promoting Smad7 expression and suppressing the TGF-β/Smad7 pathway. Knockdown of <i>circPRKCE</i> abolished AST's protective effects, confirming its pivotal role in mediating AST's anti-fibrotic activity. <b>Conclusions:</b> This study demonstrates that Astilbin alleviates radiation-induced pulmonary fibrosis via <i>circPRKCE</i> targeting the TGF-β/Smad7 pathway to inhibit EMT, suggesting AST as a potential therapeutic agent for managing this severe complication of radiotherapy.