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The ARE4 is also the site of TGF-1 action in type II alveolar cells, as TGF-1 induced the binding of Fra-1/c-Jun dimer to the internal AP-1 sequence of the ARE4 site that led to suppression of GCLC transcriptional activity [72]

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The affected patients may present loss of elasticity and tightness of the skin in a localized area, or it can be systemic, manifesting around the lips with microstomia, eating and speaking limitations, or in the fingers with sclerodactyly and vascular complications leading to functional impairment [94]