Universität zu Köln

Wang, Juan ORCID: 0000-0003-4440-9302, Eming, Sabine A. and Ding, Xiaolei (2022). Role of mTOR Signaling Cascade in Epidermal Morphogenesis and Skin Barrier Formation. Biology-Basel, 11 (6). BASEL: MDPI. ISSN 2079-7737

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Abstract

Simple Summary The skin epidermis is a stratified multilayered epithelium that provides a life-sustaining protective and defensive barrier for our body. The barrier machinery is established and maintained through a tightly regulated keratinocyte differentiation program. Under normal conditions, the basal layer keratinocytes undergo active proliferation and migration upward, differentiating into the suprabasal layer cells. Perturbation of the epidermal differentiation program often results in skin barrier defects and inflammatory skin disorders. The protein kinase mechanistic target of rapamycin (mTOR) is the central hub of cell growth, metabolism and nutrient signaling. Over the past several years, we and others using transgenic mouse models have unraveled that mTOR signaling is critical for epidermal differentiation and barrier formation. On the other hand, there is increasing evidence that disturbed activation of mTOR signaling is significantly implicated in the development of various skin diseases. In this review, we focus on the formation of skin barrier and discuss the current understanding on how mTOR signaling networks, including upstream inputs, kinases and downstream effectors, regulate epidermal differentiation and skin barrier formation. We hope this review will help us better understand the metabolic signaling in the epidermis, which may open new vistas for epidermal barrier defect-associated disease therapy. The skin epidermis, with its capacity for lifelong self-renewal and rapid repairing response upon injury, must maintain an active status in metabolism. Mechanistic target of rapamycin (mTOR) signaling is a central controller of cellular growth and metabolism that coordinates diverse physiological and pathological processes in a variety of tissues and organs. Recent evidence with genetic mouse models highlights an essential role of the mTOR signaling network in epidermal morphogenesis and barrier formation. In this review, we focus on the recent advances in understanding how mTOR signaling networks, including upstream inputs, kinases and downstream effectors, regulate epidermal morphogenesis and skin barrier formation. Understanding the details of the metabolic signaling will be critical for the development of novel pharmacological approaches to promote skin barrier regeneration and to treat epidermal barrier defect-associated diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wang, Juan UNSPECIFIED orcid.org/0000-0003-4440-9302 UNSPECIFIED Eming, Sabine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ding, Xiaolei UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-666795
DOI:	10.3390/biology11060931
Journal or Publication Title:	Biology-Basel
Volume:	11
Number:	6
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2079-7737
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR-I; KINASE-C-ALPHA; MESSENGER-RNA; MICE LACKING; S6 KINASE; KERATINOCYTE PROLIFERATION; INSULIN-RESISTANCE; TUMOR-SUPPRESSOR; MAMMALIAN TARGET; EIF-4E BP1 Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66679