International Journal of Radiation Research

en Circ-FABP5 activates the Wnt/β-catenin signaling pathway and mediates radiation-induced fibrotic response in mouse bladder fibroblast cell line via the miR-17-5p/HIF1A/CTNNB1 axis Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;">Background: Age-related bladder fibrosis (BF) is a prevalent pathological condition in the elderly, exacerbated by radiotherapy for pelvic malignancies, leading to severe bladder dysfunction. This study aimed to determine whether Circular Fatty Acid Binding Protein 5 (Circ-FABP5) activates the Wnt/β-Catenin signaling pathway to mediate radiation-induced fibrotic changes in a mouse bladder fibroblast cell line (CP-M066) through the miR-17-5p/HIF1A/CTNNB1 axis. Materials and Methods: Mouse bladder fibroblast cell line (CP-M066) was treated with varying doses of radiation (0–8 Gy) using a Shanghai Med-X Linear Accelerator and cultured with transforming growth factor (TGF)-β1 to induce fibrosis. Cell viability, apoptosis, and protein expression were assessed using MTT assay, flow cytometry, and Western blot (WB). qRT-PCR quantified miR-17-5p, HIF1A, and CTNNB1 expression. Dual-luciferase assays confirmed miR-17-5p targeting of CTNNB1. All radiation doses (0, 2, 4, 6 and 8 Gy) were evaluated to assess dose-dependent cellular and molecular responses. Results: Circ-FABP5 overexpression reduced fibroblast viability (P<0.05) and increased apoptosis (P<0.01) after 4 Gy radiation exposure. miR-17-5p expression increased by 2.3-fold, while HIF1A and CTNNB1 decreased by 60% and 55%, respectively (P<0.05). Silencing CTNNB1 inhibited fibroblast proliferation by 45% (P<0.01). Dual-luciferase assays confirmed miR-17-5p binding to CTNNB1, reducing luciferase activity by 50% (P<0.05). Radiation significantly enhanced fibrosis markers (α-SMA, collagen I) by 70% (P<0.01), which were partially reversed by Circ-FABP5 modulation. Conclusion: Circ-FABP5 regulates radiation-induced fibrotic responses in mouse bladder fibroblast cells by activating the Wnt/β-Catenin signaling pathway via the miR-17-5p/HIF1A/CTNNB1 axis. These findings provide potential molecular targets for mitigating radiation-induced bladder dysfunction.</div> Urinary bladder, fibrosis, radiotherapy, RNA, circular, wnt signaling pathway, beta catenin. 337 343 http://ijrr.com/browse.php?a_code=A-10-1-1499&slc_lang=en&sid=1 X. Wang 7900319475328460033400 7900319475328460033400 No Department of Urology, Zhejiang Hospital, Hangzhou 310030, China H. Zhou 7900319475328460033401 7900319475328460033401 No Department of Urology, Zhejiang Hospital, Hangzhou 310030, China J. Yu 7900319475328460033402 7900319475328460033402 No Department of Urology, Zhejiang Hospital, Hangzhou 310030, China J. Yan 7900319475328460033403 7900319475328460033403 No Department of Urology, Zhejiang Hospital, Hangzhou 310030, China K. Peng 7900319475328460033404 7900319475328460033404 No Department of Urology, Zhejiang Hospital, Hangzhou 310030, China H. Wen binsbb@163.com 7900319475328460033405 7900319475328460033405 Yes Department of Urology, Zhejiang Hospital, Hangzhou 310030, China