Senescent fibroblasts induce moderate stress in lung epithelial cells in vitro.
Epithelial-mesenchymal interactions contribute to functionality and integrity of the lung epithelium, which might change during ageing and associated cellular ageing. Therefore, we studied the effect of senescent versus pre-senescent lung fibroblasts (WI-38) on mitogenic and stress-protective factors in lung epithelial cells (H358). By use of conditioned medium, we found a growth promoting impact of fibroblasts compared with control medium from epithelial cells associated with activation of ERK1/2, Akt, p70S6K, and EGF receptor. Although senescent fibroblasts mediated similar growth stimulation compared with pre-senescent cells, we observed less protection against spontaneous mitochondrial dysfunction in vitro, higher production of reactive oxygen species and activation of copper/zinc superoxide dismutase. Moreover, senescent cells induced activation of caspase-3/7 in epithelial cells, which was associated with down-regulation of the caspase-inhibitory protein XIAP. In summary, senescent lung fibroblasts induce moderate stress in lung epithelial cells in vitro without affecting growth signaling.
Bartling
Babett
B
Department of Cardio-thoracic Surgery, Martin Luther University Halle-Wittenberg, Ernst-Grube-Street 40, 06120 Halle (Saale), Germany. babett.bartling@medizin.uni-halle.de
Rehbein
Grit
G
Silber
Rolf-Edgar
RE
Simm
Andreas
A
D002450:Cell Communication / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology; D015398:Signal Transduction / Q000502:physiology
D017077:Culture Media, Conditioned; D017382:Reactive Oxygen Species