Insights into the role of endoplasmic reticulum stress in skin function and associated diseases

• Published in: The FEBS journal Vol. 286; no. 2; pp. 413 - 425
• Main Authors: Park, Kyungho, Lee, Sang Eun, Shin, Kyong‐Oh, Uchida, Yoshikazu
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2019
• Subjects: Accumulation; Animals; Apoptosis; Cell death; Darier's disease; Diseases; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - pathology; Endoplasmic Reticulum Stress; Humans; Irradiation; Keratosis; Melanoma; Pathogenesis; Protein Folding; Proteins; Rosacea; Signal Transduction; Skin - metabolism; skin disease; Skin diseases; Skin Diseases - physiopathology; skin function; Stress; Ultraviolet radiation; Unfolded Protein Response; Vitiligo; unfolded protein response; skin disease; endoplasmic reticulum stress; skin function
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.14739

Endoplasmic reticulum (ER) stress is a mechanism that allows the protection of normal cellular functions in response to both internal perturbations, such as accumulation of unfolded proteins, and external perturbations, for example redox stress, UVB irradiation, and infection. A hallmark of ER stress is the accumulation of misfolded and unfolded proteins. Physiological levels of ER stress trigger the unfolded protein response (UPR) that is required to restore normal ER functions. However, the UPR can also initiate a cell death program/apoptosis pathway in response to excessive or persistent ER stress. Recently, it has become evident that chronic ER stress occurs in several diseases, including skin diseases such as Darier's disease, rosacea, vitiligo and melanoma; furthermore, it is suggested that ER stress is directly involved in the pathogenesis of these disorders. Here, we review the role of ER stress in skin function, and discuss its significance in skin diseases. Physiological levels of endoplasmic reticulum (ER) stress are required for modulation of normal cellular functions in the skin, including keratinocyte differentiation, through the unfolded protein response (UPR). However, persistent or excessive levels of ER stress induce cell death and apoptosis signalling. Growing evidence describes chronic ER stress in several cutaneous diseases e.g., Darier’s disease, rosacea, vitiligo, and melanoma. In this review, we discuss the role of ER stress in normal skin function and disease.