Proliferation, migration and inflammation-related signaling pathways activated in THBS4-stimulated keratinocytes characterize both wound healing and atopic dermatitis

Atopic dermatitis, which is a common inflammatory skin disease characterized by persistent epidermal barrier dysfunction, is a systemic health burden reducing overall quality of life of the person. Recently, we showed that the nonstructural extracellular matrix molecule Thrombospondin-4 (THBS4) was upregulated in psoriatic skin lesions by more than 2-fold. In addition, THBS4 contributed to both skin regeneration and wound healing in vitro and in vivo. In the present work we found that THBS4 is also abundantly expressed in atopic dermatitis (AD) patient skin biopsies. By using a proteotransciptomic approach we show that stimulation of primary keratinocytes with THBS4 activates multiple factors, including inflammation, migration, proliferation, keratinocyte differentiation, by which THBS4 could participate in AD progression and contribute to the wound healing process.