Chapters authored
Genetic Abnormalities, Melanosomal Transfer, and Degradation inside Keratinocytes Affect Skin Pigmentation
Skin pigmentation is a specific and complex mechanism that occurs as a result of the quantity and quality of melanin produced, as well as the size, number, composition, mode of transfer, distribution, and degradation of the melanosomes inside keratinocytes and the handling of the melanin product by the keratinocyte consumer. Melanocyte numbers typically remain relatively constant. Melanin synthesis, melanosome maturation, and melanoblast translocation are considered to be responsible for hereditary pigmentary disorders. Keratinocytes play a significant role in regulating the adhesion, proliferation, survival, and morphology of melanocytes. In the epidermis, each melanocyte is surrounded by 30–40 keratinocytes through dendrites and transfers mature melanosomes into the cytoplasm of keratinocytes, which are then digested. Melanocytes are believed to transfer melanosomes to neighboring keratinocytes via exocytosis-endocytosis, microvesicle shedding, phagocytosis, or the fusion of the plasma membrane, protecting skin cells against ultraviolet (UV) damage by creating a physical barrier (cap structure) over the nucleus. An understanding of the factors of melanocytes and keratinocytes that induce pigmentation and the transfer mechanism of melanosomes to keratinocytes and how genetic abnormalities in keratinocytes affect pigmentary skin disorders will help us to elucidate hereditary pigmentary disorders more transparently and provide a conceptual framework for the importance of keratinocytes in the case of pigmentary disorders.
Part of the book: Keratinocyte Biology
Keratinocytes in Skin Disorders: The Importance of Keratinocytes as a Barrier
Keratinocytes are the major structural component of the epidermis. They differentiate from the basal through spinous to granular layers, and abrupt loss of nucleus pushes them to differentiate into cornified layers, which exfoliates as scales. Differentiation process is tightly controlled by the organized expression of transcription factors and other regulators, which sustains the physiological function of the skin barrier. The genetic abnormality of the molecules expressed in this pathway causes hereditary skin disorders and defects in barrier function. Ichthyosis is caused by keratins, enzymes, and structural proteins involved in lipid metabolism and cornified envelope formation. Atopic dermatitis seemed to be an immune-oriented disease, but the recent finding revealed filaggrin as a causative factor. Keratinocytes respond to acute injury by releasing alarmins. IL-33 is one of such alarmins, which provoke Th2-type inflammation. IL-33 works as a cytokine and, at the same time, as nuclear protein. IL-33 has double-faced nature, with pro- and anti-inflammatory functions. Epidermis, covering the entire body, should stay silent at minor insults, while it should provoke inflammatory signals at emergency. IL-33 and other double-faced molecules may play a role in fine tuning the complexed function of epidermal keratinocytes to maintain the homeostasis of human body.
Part of the book: Keratinocyte Biology