Neuroendocrine signaling in the skin with a special focus on the epidermal neuropeptides.

A. Slominski,R. Slominski,C. Raman,J. Chen,M. Athar,C. Elmets

Published 2022 in American Journal of Physiology - Cell Physiology

ABSTRACT

The skin, which is comprised of the epidermis, dermis, and subcutaneous tissue, is the largest organ in the human body and it plays a crucial role in the regulation of the body's homeostasis. These functions are regulated by local neuroendocrine and immune systems with a plethora of signaling molecules produced by resident and immune cells. In addition, neurotransmitters, endocrine factors, neuropeptides, and cytokines released from nerve endings play a central role in the skin responses to stress. These molecules act on the corresponding receptors in an intra-, juxta-, para- or autocrine fashion. The epidermis as the outer most component of skin forms a barrier directly protecting against environmental stressors. This protection is assured by an intrinsic keratinocyte differentiation program, pigmentary system and local nervous, immune, endocrine, and microbiome elements. These constituents communicate cross-functionally among themselves and with corresponding systems in the dermis and hypodermis to secure the basic epidermal functions to maintain local (skin) and global (systemic) homeostasis. The neurohormonal mediators and cytokines used in these communications regulate physiological skin functions separately or in concert. Disturbances in the functions in these systems lead to cutaneous pathology that includes inflammatory (psoriasis, allergic or atopic dermatitis) and keratinocytic hyperproliferative disorders (seborrheic and solar keratoses), dysfunction of adnexal structure (hair follicles, eccrine and sebaceous glands), hypersensitivity reactions, pigmentary disorders (vitiligo, melasma and hypo- or hyperpigmentary responses, premature aging, and malignancies (melanoma and non-melanoma skin cancers). These components preserve skin integrity and protect against skin pathologies.

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