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The important role of lipids in the epidermis and their role in the formation and maintenance of the cutaneous barrier
Biochimica et Biophysica Acta 1841 (2014) 279
Contents lists available at ScienceDirect
Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbalip
Preface
The important role of lipids in the epidermis and their role in the formation and maintenance of the cutaneous barrier
Lipid metabolism in the epidermis has been an area of research that has been largely ignored by the community of scientists studying lipid metabolism. However, as presented in this special issue, lipid metabolism in the epidermis has unique features and plays an essential role that is required for terrestrial life. The permeability barrier that is localized in the stratum corneum layer of the epidermis is composed of lipids, predominantly cholesterol, ceramides, and free fatty acids, organized into structurally unique lamellar bilayers. This permeability barrier prevents the movement of water and electrolytes from the internal milieu to the external, while simultaneously preventing the entry of toxic chemicals from the external environment into the body. In addition to their role in the permeability barrier, lipids in the epidermis also play a key role in providing a barrier to the colonization and invasion of pathogenic microorganisms. Without a competent permeability barrier, survival is compromised as illustrated by the clinical abnormalities seen in markedly premature infants and burn patients, where these barriers are dysfunctional. In this special issue a series of articles discuss in detail cholesterol, fatty acid, and ceramide synthesis and metabolism in the epidermis, and how these processes culminate in the formation of lamellar bodies that deliver lipids from the keratinocytes to the extracellular matrix of the stratum corneum to mediate barrier function. In addition, the impact of defects and errors in metabolism on the formation of lamellar bodies and cutaneous barrier function is discussed. It is hoped that this special issue will stimulate other investigators to develop an interest in epidermal lipid metabolism and apply their special skills and knowledge to further unravel the pathways that lead to a normal functioning epidermis and to help develop treatments for patients with abnormalities in epidermal lipid metabolism.
Dr. Peter M. Elias is a Staff Physician at the VA Medical Center, and a professor in the Department of Dermatology, UCSF, San Francisco. He is largely responsible for the present wealth of knowledge on both the structure and myriad functions of mammalian stratum corneum, beginning with research in the 1970's that dispelled the myth of the stratum corneum as a 'dead, keratinized, basket-weave' structure, while also establishing the 'brick and mortar' model of the stratum corneum. Because of his highly-productive, 30+ year collaboration with Dr. Kenneth Feingold, the co-editor of this special issue of BBA, the stratum corneum is now viewed as a metabolically active biosensor that modulates specific metabolic responses in the epidermis, following alterations in the external environment. The resultant 'outside-in' concept of the barrier as a prime mover in the pathogenesis of inflammatory skin diseases has also been a focus of Dr. Elias' work, contributing to the current, widelyrecognized view of skin barrier dysfunction as a 'driver' of disease pathogenesis. This line of inquiry led to the development of several forms of 'pathogenesis-based' therapy that are now part of clinicians' armamentarium in treating these disorders.
Kenneth Feingold1 Metabolism Section, VA Medical Center and Department of Medicine, University of California, San Francisco 4150 Clement Street San Francisco, CA 94121 USA E-mail address: [email protected]. Peter Elias2 Dermatology Service, VA Medical Center 4150 Clement Street San Francisco, CA 94121 USA E-mail address: [email protected].
Dr. Feingold is a Professor of Medicine at the University of California San Francisco and a staff physician and Chief of the Endocrine Clinic at the San Francisco VA Medical Center. He obtained his BS degree from the University of Wisconsin and his MD degree from the State University of New York-Upstate Medical Center in Syracuse. He completed his internship and residency in Internal Medicine at the University of Wisconsin and a fellowship in Endocrinology and Metabolism at the University of California San Francisco. His research interests are in the role of lipid metabolism in the epidermis for the formation of a permeability barrier and in the effect of inflammation on lipid and lipoprotein metabolism. Dr. Feingold is an associate editor for the Journal of Lipid Research, the Journal of Investigative Dermatology, and Dermato-Endocrinology.
1 2
1388-1981/$ – see front matter © 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.bbalip.2013.12.004
Tel.: +1 415 750 2005. Tel.: +1 415 750 2091.
Contents lists available at ScienceDirect
Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbalip
Preface
The important role of lipids in the epidermis and their role in the formation and maintenance of the cutaneous barrier
Lipid metabolism in the epidermis has been an area of research that has been largely ignored by the community of scientists studying lipid metabolism. However, as presented in this special issue, lipid metabolism in the epidermis has unique features and plays an essential role that is required for terrestrial life. The permeability barrier that is localized in the stratum corneum layer of the epidermis is composed of lipids, predominantly cholesterol, ceramides, and free fatty acids, organized into structurally unique lamellar bilayers. This permeability barrier prevents the movement of water and electrolytes from the internal milieu to the external, while simultaneously preventing the entry of toxic chemicals from the external environment into the body. In addition to their role in the permeability barrier, lipids in the epidermis also play a key role in providing a barrier to the colonization and invasion of pathogenic microorganisms. Without a competent permeability barrier, survival is compromised as illustrated by the clinical abnormalities seen in markedly premature infants and burn patients, where these barriers are dysfunctional. In this special issue a series of articles discuss in detail cholesterol, fatty acid, and ceramide synthesis and metabolism in the epidermis, and how these processes culminate in the formation of lamellar bodies that deliver lipids from the keratinocytes to the extracellular matrix of the stratum corneum to mediate barrier function. In addition, the impact of defects and errors in metabolism on the formation of lamellar bodies and cutaneous barrier function is discussed. It is hoped that this special issue will stimulate other investigators to develop an interest in epidermal lipid metabolism and apply their special skills and knowledge to further unravel the pathways that lead to a normal functioning epidermis and to help develop treatments for patients with abnormalities in epidermal lipid metabolism.
Dr. Peter M. Elias is a Staff Physician at the VA Medical Center, and a professor in the Department of Dermatology, UCSF, San Francisco. He is largely responsible for the present wealth of knowledge on both the structure and myriad functions of mammalian stratum corneum, beginning with research in the 1970's that dispelled the myth of the stratum corneum as a 'dead, keratinized, basket-weave' structure, while also establishing the 'brick and mortar' model of the stratum corneum. Because of his highly-productive, 30+ year collaboration with Dr. Kenneth Feingold, the co-editor of this special issue of BBA, the stratum corneum is now viewed as a metabolically active biosensor that modulates specific metabolic responses in the epidermis, following alterations in the external environment. The resultant 'outside-in' concept of the barrier as a prime mover in the pathogenesis of inflammatory skin diseases has also been a focus of Dr. Elias' work, contributing to the current, widelyrecognized view of skin barrier dysfunction as a 'driver' of disease pathogenesis. This line of inquiry led to the development of several forms of 'pathogenesis-based' therapy that are now part of clinicians' armamentarium in treating these disorders.
Kenneth Feingold1 Metabolism Section, VA Medical Center and Department of Medicine, University of California, San Francisco 4150 Clement Street San Francisco, CA 94121 USA E-mail address: [email protected]. Peter Elias2 Dermatology Service, VA Medical Center 4150 Clement Street San Francisco, CA 94121 USA E-mail address: [email protected].
Dr. Feingold is a Professor of Medicine at the University of California San Francisco and a staff physician and Chief of the Endocrine Clinic at the San Francisco VA Medical Center. He obtained his BS degree from the University of Wisconsin and his MD degree from the State University of New York-Upstate Medical Center in Syracuse. He completed his internship and residency in Internal Medicine at the University of Wisconsin and a fellowship in Endocrinology and Metabolism at the University of California San Francisco. His research interests are in the role of lipid metabolism in the epidermis for the formation of a permeability barrier and in the effect of inflammation on lipid and lipoprotein metabolism. Dr. Feingold is an associate editor for the Journal of Lipid Research, the Journal of Investigative Dermatology, and Dermato-Endocrinology.
1 2
1388-1981/$ – see front matter © 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.bbalip.2013.12.004
Tel.: +1 415 750 2005. Tel.: +1 415 750 2091.