Inflammation drives TGFß1 activation via the avß6 integrin-mechanotransduction pathway in human skin

Transforming growth factor ß (TGFß) is a critical regulator of skin homeostasis and is implicated in skin inflammation, including psoriasis. We investigated the molecular mechanisms of TGFß1 regulation during cutaneous inflammation using reconstructed human epidermis. We report a mechanosensitive positive feedback loop, that occurs downstream of inflammatory stimuli and involves TGFß-mediated activation of mechanotransduction pathways, further promoting avß6 integrin-dependent TGFß1 activation in keratinocytes. Overall design: N/TERT-1 keratinocytes were cultured to create 3D reconstituted human epidermis model (10 days at the air-liquid interphase), and then stimulated with 10ng/ml TGFß1 for 3 days.