Synergy of understanding dermatologic disease and epidermal biology

Abstract

Dermatologic disease, although seldom life threatening, can be extremely disfiguring and interfere with the quality of life. In addition, as opposed to other organs, just the aging of skin and its adnexal structure the hair follicle can result in cosmetic concerns that affect most of us. The articles in this dermatology Review Series demonstrate recent progress in understanding the cell biology and molecular pathophysiology of the epidermis and hair follicles, which harbor keratinocyte and melanocyte stem cells. They reveal a dynamic relationship between research and clinical care: knowledge of dermatologic disease has facilitated the understanding of the biology of the epidermis and, in turn, progress in basic science has informed our understanding of disease. This type of synergy is a profound strength of clinical research of the type that the JCI is dedicated to publishing. IntroductionThe Reviews in this series highlight the progress in understanding several dermatologic diseases that are particularly important because they are common and/or disfiguring. Kubo et al. (1) highlight recent major progress in understanding the pathophysiology of atopic dermatitis (Figure 1), a disease both very common (estimates are 10%-20% prevalence in children; ref.2) and potentially severe and difficult to deal with for both patients and parents. Myung and Ito (3) discuss recent progress in understanding the bulge of the hair follicle and its importance in harboring both keratinocyte and melanocyte stem cells. Understanding the cell biology of the bulge is important for dissecting the pathophysiology of skin cancer-like basal cell carcinoma (BCC) as well as the potentially disfiguring disease vitiligo (Figure 2). In addition, the melanocyte stem cell contributes to hair pigment. Insights into this stem cell may help us understand the physiologic process of the graying of hair with age. Normal graying of hair, although not a disease, is of great concern to millions of people, probably because pigment in hair is an indication of youth (Figure 3). Finally, Kasper et al. (4) and Ratushny et al. (5) discuss new aspects of the pathophysiology of skin cancers. Not only are cancers of the skin some of the most common cancers in humans, but they can be terribly disfiguring if left untreated (Figure 4).

Melanocyte stem cells as potential therapeutics in skin disorders

“…Thus, it is plausible that modulating the MC1R pathway might contribute to improvement to pigmentary disorders such as vitiligo, melasma, or postinflammatory hyper/hypopigmentation [94] . Furthermore, other clinical and cosmetic implications of MelSCs have been postulated in a review by Stanley [95] . Considering stem cell anatomy and biology, permanent hair removal by electrolysis or laser treatment should be focused on eliminating the hair bulge, even though there is some difficulty in targeting selectively the bulge areas.…”

Structural and Functional Changes and Possible Molecular Mechanisms in Aged Skin

“…Histological changes in chronologically aged skin are characterized by decreased recovery capacity, altered permeability of the stratum corneum, epidermal atrophy particu-2 of 17 larly affecting the stratum spinosum, and decreased amounts of fibroblasts and collagen in the dermis (Figure 1). The stratum corneum consists of corneocytes, which are anulceated keratinocytes retaining keratin filaments within a filaggrin matrix and surrounded by a cornified lipid envelope; they organize into a brick-and-mortar formation within the ECM, forming lipid-rich membranes [6]. A recent biochemical study using cadaveric donors found that the stratum corneum, especially the keratin fibers in chronologically aged skin, stiffens with aging.…”

“…Stratum corneum [6][7][8] Epidermal atrophy [9,10] Langerhans cells [11] Dermis Fibroblast senescence [13,14,44] Collagen structure [15][16][17][18]43,44] Elastic fibers [22,23] Photoaging Epidermal thickness [25,26] Cell atypism [27] Solar elastosis [32,34,36,38,40]…”

The Pathobiology of Skin Aging

“…The stratum corneum, the outermost layer of the epidermis, consists of corneocytes arranged in compact sheets that are embedded in an extracellular matrix derived from lamellar granules forming lipid-rich membranes. 10,11 This cornified layer acts as the outermost interface between the atmosphere and the underlying epidermal and dermal tissues. The thickness of the stratum corneum can be dynamic throughout life, and it can become thickened in response to various insults or inflammatory conditions.…”