Akademik Veri Yönetim Sistemi
International Adana Scientific Research and Innovation Congress, Adana, Türkiye, 3 - 05 Kasım 2025, (Yayınlanmadı)
Introduction and Aim: Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and fatal interstitial lung disease. Myofibroblasts, the main effector cells in IPF, produce and secrete excessive extracellular matrix (ECM) components, leading to their accumulation in lung interstitium. Current anti-fibrotic approaches target fibroblast/myofibroblast proliferation, differentiation, or ECM degradation. In this study, colchicine (CLC) was evaluated as an alternative anti-fibrotic strategy. By disrupting microtubule-mediated trafficking of ECM-containing vesicles, CLC was hypothesized to induce intracellular ECM accumulation, creating cellular stress that could trigger antifibrotic responses in human lung myofibroblasts.
Materials and Methods: Human lung fibroblasts (MRC-5) were divided into four groups: I) control, II) TGF-β (1 ng/ml)-induced differentiation, III) CLC treatment (0.01 µM at 0 and 24 h), and IV) TGF-β+CLC. Cells were collected at 24, 48, and 72 h. CLC efficacy was assessed by MTT assay, α-tubulin immunofluorescence, and BrdU proliferation test. Myofibroblast differentiation (α-SMA, collagen, fibronectin), apoptosis (active caspase-3, Bax, survivin), autophagy (Beclin-1, ATG5, LC3B I/II, LAMP2), and lysosomal activity (neutral red uptake) were analyzed. Ultrastructural changes were examined by transmission electron microscopy.
Results: TGF-β significantly increased α-SMA, collagen, and fibronectin expression and secretion, while reducing proliferation and apoptotic/autophagic signaling. CLC treatment depolymerized microtubules, leading to intracellular ECM accumulation and reduced ECM secretion, especially at 72 h (p<0.05). TGF-β+CLC co-treatment further suppressed myofibroblast differentiation and proliferation. These cells showed reduced caspase-3, Bax, and survivin levels, alongside activation of autophagic markers, particularly LC3B I/II conversion (p<0.001–0.05). Electron microscopy confirmed increased vesicular accumulation and autophagic vacuole formation.
Conclusion: Colchicine inhibited microtubule-mediated ECM trafficking, suppressed myofibroblast differentiation and proliferation, and promoted autophagy in TGF-β-stimulated fibroblasts. These findings suggest a potential antifibrotic role for colchicine via induction of cellular stress and autophagic response.
Keywords: Anti-fibrotic effect, Cholchicine, Myofibroblast differentiation, Autophagy, Pulmonary fibrosis.