TGF-β isoform release and activation during in vitro bronchial epithelial wound repair

WJ Howat, ST Holgate… - American Journal of …, 2002 - journals.physiology.org
WJ Howat, ST Holgate, PM Lackie
American Journal of Physiology-Lung Cellular and Molecular …, 2002journals.physiology.org
Restitution of an epithelial layer after environmental or biological damage is important to
maintain the normal function of the respiratory tract. We have investigated the role of
transforming growth factor (TGF)-β isoforms in the repair of layers of 16HBE 14o− bronchial
epithelial-derived cells after damage by multiple scoring. ELISA showed that both latent TGF-
β1 and TGF-β2 were converted to their active forms 2 h after wounding. Time-lapse
microscopy showed that the addition of TGF-β1, but not TGF-β2, progressively increased the …
Restitution of an epithelial layer after environmental or biological damage is important to maintain the normal function of the respiratory tract. We have investigated the role of transforming growth factor (TGF)-β isoforms in the repair of layers of 16HBE 14o bronchial epithelial-derived cells after damage by multiple scoring. ELISA showed that both latent TGF-β1 and TGF-β2 were converted to their active forms 2 h after wounding. Time-lapse microscopy showed that the addition of TGF-β1, but not TGF-β2, progressively increased the rate of migration of damaged monolayers at concentrations down to 250 pg/ml. This increase was blocked by addition of a neutralizing TGF-β1 antibody. Phase-contrast microscopy and inhibition of proliferation with mitomycin C showed that proliferation was not required for migration. These results demonstrate that conversion of latent to active TGF-β1 and TGF-β2 during in vitro epithelial wound repair occurs quickly and that TGF-β1 speeds epithelial repair. A faster repair may be advantageous in preventing access of environmental agents to the internal milieu of the lung although the production of active TGF-β molecules may augment subepithelial fibrosis.
American Physiological Society