Abstract
Human tissue Kallikrein-related peptidases (hKLKs) are serine proteases distributed in several tissues that are involved in several biological processes. In skin, many are responsible for skin desquamation in the Stratum Corneum (SC) of the epidermis, specially hKLK5, hKLK7, hKLK6, hKLK8, and hKLK14. In SC, hKLKs cleave proteins of corneodesmosomes, an important structure responsible to maintain corneocytes attached. As part of skin desquamation, hKLKs are also involved in skin diseases with abnormal desquamation and inflammation, such as Atopic Dermatitis (AD), psoriasis, and the rare disease Netherton Syndrome (NS). Many studies point to hKLK overexpression or overactive in skin diseases, and they are also part of the natural skin inflammation process, through the PAR2 cleavage pathway. Therefore, the control of hKLK activity may offer successful treatments for skin diseases, improving the quality of life in patients. Diseases like AD, Psoriasis, and NS have an impact on social life, causing pain, itchy and mental disorders. In this review, we address the molecular mechanisms of skin desquamation, emphasizing the roles of human tissue Kallikrein-related peptidases, and the promising therapies targeting the inhibition of hKLKs.
Highlights
The skin is the largest organ in the human body, composed of multiple layers of cells, and holds the first protection of our body against the outside world, in addition to regulation of body temperature, water loss, and production of vitamin D [1–3]
The role of human Kallikrein-related peptidases is yet to be completely resolved, but a study comparing healthy subjects and patients with Psoriasis showed aberrant levels of Human tissue Kallikrein-related peptidases (hKLKs) in psoriatic lesions [47]. hKLK6, hKLK8, hKLK10, and hKLK13 were in higher levels at the serum of patients with untreated Psoriasis, and a correlation between the levels of these Kallikreins and Severity Index was reported [47]. hKLK6 and hKLK8 are upregulated in psoriatic lesions [47], and it was demonstrated that hKLK8 is important to the development of Munro’s microabscess in the epidermis, a structure formed by an increased number of T-lymphocytes, macrophages, mast cells, and neutrophilic granulocytes [43]
Human tissue Kallikrein-related peptidases are involved in several biological processes, including skin desquamation and inflammation
Summary
Peptidases Are Targets for the Treatment of Skin Desquamation Diseases. Human tissue Kallikrein-related peptidases (hKLKs) are serine proteases distributed in several tissues that are involved in several biological processes. As part of skin desquamation, hKLKs are involved in skin diseases with abnormal desquamation and inflammation, such as Atopic Dermatitis (AD), psoriasis, and the rare disease Netherton Syndrome (NS). Many studies point to hKLK overexpression or overactive in skin diseases, and they are part of the natural skin inflammation process, through the PAR2 cleavage pathway. The control of hKLK activity may offer successful treatments for skin diseases, improving the quality of life in patients. We address the molecular mechanisms of skin desquamation, emphasizing the roles of human tissue Kallikrein-related peptidases, and the promising therapies targeting the inhibition of hKLKs
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