Such aberrant layers in the SC consisted of an upper SC without filaggrin staining and a lower SC stained by anti-filaggrin Ab with the accumulation of aberrant dimeric and trimeric filaggrin, i.e. premature profilaggrin processing (Figs 5B and 8).
As described in the Introduction section, filaggrin is thought to have two major functions: the formation of keratin microfibrils in the lower SC and the production of NMFs in the upper SC (Rawlings & Harding, 2004; Fig 8).
In the upper SC, filaggrin-2 is deiminated and degraded by calpain 1.
Similar to filaggrin, filaggrin-2 has been suspected to be degraded to free amino acids in the upper SC.
Their presence in the upper SC suggested that they also might have a role in SC acidification, in addition to sPLA2-IB that has previously been thought to function in that regard.
22 The increasing acidity seen in the upper SC layers derives from an increasing number of uniformly acidic microdomains rather that the increasing acidity of a fixed number of individual microdomains.
It is possible that dry skin of SASP−/− hairless mice is derived from the lower SC where aberrantly processed filaggrin accumulates, but not from the upper SC where the end-products of filaggrin (NMFs) are located.
Keratin-bound filaggrin is citrullinated and further degraded into amino acids, which constitute a part of the natural moisturizing factor (NMF) in the upper SC (Tarcsa et al, 1996; Mechin et al, 2005; Nachat et al, 2005; Ishida-Yamamoto et al, 2002; Denecker et al, 2007; Kamata et al, 2009).
