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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
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X. Wang   , H. Zhou , J. Yu , J. Yan , K. Peng , H. Wen |
| Department of Urology, Zhejiang Hospital, Hangzhou 310030, China , binsbb@163.com |
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Abstract: (21 Views) |
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. |
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| Keywords: Urinary bladder, fibrosis, radiotherapy, RNA, circular, wnt signaling pathway, beta catenin. |
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Full-Text [PDF 881 kb]
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Type of Study: Original Research |
Subject:
Radiation Biology
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