Fig. (2) Hypothetical modes of activation of the Notch pathway in systemic sclerosis. ROS produced during the ischemiareperfusion phenomena or through the injection of HOCl in mice, could activate the metalloprotease ADAM17, thus indirectly triggering the release of NICD. NICD can then translocate to the nucleus and activate the transcription of its target genes leading to the development of fibrosis.