*7.2.1 Keratin 14*

K14 is an important IF expressed in the basal KCs which decide the fate of epidermis by protecting it from any mechanical or chemical disturbances. Normallay, basal layer contains epidermal stem cells and TA cells that proliferate into KCs. The epidermal stem cells and TA cells expressed keratin K5/K14 which destined the cells to proliferate into KC [32].

In psoriatic skin biopsy, K14 expression was considerably higher than in normal epidermis [33–35]. However, MTX reduced the expressions of K14 in lesional skin biopies by increasing Phosphorylated form of p53 expression [201]. Studies have shown that p53 enhance the notch signaling [202], which leads to modulation and normalization of K14 expression to K10 differentiation marker. Thus, decrease in K14 expression leads to reduction in cell proliferation, decrease in phospho-Akt levels, increase in activated Notch1 levels, and increase in levels of KC differentiation markers [39] and also increased in p21 and p27 levels, which are known to be direct targets of Notch1 signals. Activation of p21 and p27 leads to cell cycle arrest [191, 203] which leads to inhibition of hyperproliferating KCs in psoriasis.
