Early signs of lung fibrosis after in vitro treatment of rat lung slices with CdCl2 and TGF-?1

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Abstract
Precision-cut rat lung slices have been employed in combination with an extensive immunohistochemistry of paraffin-embedded slices for monitoring of early pathohistological changes after exposure to CdCl2/TGF-β1. Three days of CdCl2 exposure in combination with TGF-β1 seem to be sufficient to induce lung injury with alterations similar to changes observed in early lung fibrogenesis: (1) extracellular matrix accumulation and myofibroblast transdifferentiation (Sirius red staining, collagen type IV, α-smooth muscle actin), (2) type I cell injury with loss of type I cell antigens (T1α antigen, aquaporin-5, RAGE), (3) increased apoptosis of pulmonary cells (active caspase-3, vimentin cleavage product V1 of caspase-9), and (4) activation of microvascular endothelial cells (podocalyxin, caveolin-1). Western blot analysis confirmed the increasing amount of α-smooth muscle actin, the loss of T1α antigen, and the increase in caveolin-1 immunoreactivity. The explant culture using CdCl2/TGF-β1 provides a suitable tool for the study of other factors involved in pulmonary pathology including transcription factors, cytokines, and other metabolites involved in early stages of fibrogenesis.