Activation and upregulation of keratinocyte and epidermal transglutaminases are associated with depletion of their substrates in psoriatic lesions.

OBJECTIVE

Psoriasis is a chronic skin disorder caused by abnormal interactions between epidermal and immune cells. Thus, the interplay between the proliferation and differentiation of epidermal components should be tightly regulated to protect against psoriasis. The differentiation process is primarily controlled by transglutaminases (TGs). However, studies on TG enzymes and their molecular alterations in psoriatic skin lesions are limited. Therefore, this study aimed to investigate TG activity and gene and protein expression in human psoriatic and normal skin tissues.

MATERIALS AND

METHODS

Keratinocyte TG (TG1), and epidermal TG (TG3) activity, localization, protein levels, and gene expression in human psoriatic skin were determined by immunohistochemistry and RT-qPCR. The expression of TG substrates (loricin and involucrin - IVL) was also investigated using RT-qPCR.

RESULTS

TG1 and TG3 enzymatic activities and gene expression were significantly higher in psoriatic skin tissue than in normal skin tissue. However, both TGs were present in the same location and were equally highly expressed. Moreover, the expression of two TG substrates (loricin and involucrin) was significantly decreased compared to that in psoriatic and healthy skin samples.

CONCLUSIONS

The activation and upregulation of TG1 and TG3 result from the depletion of their substrates (loricin and involucrin), both of which play a major role in the pathogenicity of psoriatic skin tissue and are necessary for proper skin development.