Keratin filaments under CE fill the cell to maintain the integrity of the cell shape. SPRR acts not only as a shield against ROS but also promotes wound healing. SPRR was also reported to be expressed in keratinocyte migration in the epidermis. SPRR plays an important role of battling ROS in healthy skin.
In particular, SPRR-4 showed stronger antioxidant action than loricrin. Such benefits are associated with the rich cysteine content in this protein, its direct reaction to ROS and covalent bonds between its molecules. Expression of SPRR-4 was shown to increase after UV exposure, which is related to hyperkeratinization due to chronic UV exposure. SPRR-4 infiltrates into the weakened CE and helps maintain the CE barrier to protect the epidermis against UV rays.
Keratin Turnover
In X-linked ichthyosis, natural loss of keratinocytes is inhibited by preventing hydrolysis of cholesterol sulfate in the stratum corneum. While excessive cholesterol sulfate prevents keratin loss, its hydrolysis promotes it. Protease include SC tryptic enzyme and SC chymotryptic enzyme which breaks desmosome and triggers stratum corneum turnover. Cholesterol sulfate inhibit involucrin cross-linking by transglutaminase as well as esterification of ω-hydroxyceramide and involurcin to cause retention hyperkeratosis.
Keratin
It is often thought that dryness causes keratin buildup but in reality, keratin forms from various abnormalities of the skin. Keratinocytes fall in very small invisible pieces. If this natural turnover process is disturbed, keratin builds up on the skin surface and creates visible, dry texture. The water content of the stratum corneum is important for preventing this.
Water-soluble intracellular substances such as natural moisturizing factors (NMFs) and intercellular lipids are crucial for maintaining the water content of stratum corneum and adjusting TEWL. NMFs consist of amino acids and its byproducts (pyrrolidone carboxylic acid and urocanic acid), lactic acid, urea, and monosaccharides. The amino group of NMFs form from proteinase degradation of filaggrin. Keratin turnover and hydrolase process of forming NMFs are important strategies of keeping the stratum corneum hydrated. The decrease in NMFs in the stratum corneum is caused by both internal and external factors.
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Harsh soap can damage the intercellular lipids or abnormal cell differentiation can also lead to a drop in NMFs. Ichthyosis develops from filaggrin deficiency where lack of NMFs dries the skin. In aged skin, abnormal lipogenesis (cholesterol) can cause xeroderma. The degree of keratin buildup varies depending on the degree of damage to the skin barrier.
The skin barrier can be compromised when the intercellular lipids of the stratum corneum or CE under them are damaged. Epidermolytic hyperkeratosis develops from genetic defects in suprabasal keratin 1 and 10 which weakens keratinocytes and makes the skin vulnerable to frequent blistering and excessive keratin buildup.
Release of abnormal LGs or a drop in lipid lamella within the stratum corneum can also damage the barrier. In many inflammatory diseases, abnormal epidermal differentiation often weakens keratinocytes and intercellular lipids which leads to keratin buildup.
-To be continued
