Murine Epidermal Ceramide Synthase 4 Is a Key Regulator of Skin Barrier Homeostasis

Peters, Franziska; Tellkamp, Frederik; Brodesser, Susanne; Wachsmuth, E.; Tosetti, Bettina; Karow, Ulrike; Bloch, Wilhelm; Utermöhlen, Olaf; Krönke, Martin; Niessen, Carien M.

doi:10.1016/j.jid.2020.02.006

Cited by 12 publications

(15 citation statements)

References 46 publications

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“…This effect is notable because CerS4 catalyzes the synthesis of shorter-chained ceramide species that are not directly involved in the structure of the barrier. These species or other lipids indirectly affected by CerS4 knockdown may thus be involved in signaling events that are necessary for epidermal homeostasis ( Peters et al, 2020 ).…”

Section: Under-recognized Actors – the Role Of Lipid Signaling In Epidermal Homeostasismentioning

confidence: 99%

Mammalian Epidermis: A Compendium of Lipid Functionality

Rudan

Watt

2022

Front. Physiol.

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Mammalian epidermis is a striking example of the role of lipids in tissue biology. In this stratified epithelium, highly specialized structures are formed that leverage the hydrophobic properties of lipids to form an impermeable barrier and protect the humid internal environment of the body from the dry outside. This is achieved through tightly regulated lipid synthesis that generates the molecular species unique to the tissue. Beyond their fundamental structural role, lipids are involved in the active protection of the body from external insults. Lipid species present on the surface of the body possess antimicrobial activity and directly contribute to shaping the commensal microbiota. Lipids belonging to a variety of classes are also involved in the signaling events that modulate the immune responses to environmental stress as well as differentiation of the epidermal keratinocytes themselves. Recently, high-resolution methods are beginning to provide evidence for the involvement of newly identified specific lipid molecules in the regulation of epidermal homeostasis. In this review we give an overview of the wide range of biological functions of mammalian epidermal lipids.

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Section: Under-recognized Actors – the Role Of Lipid Signaling In Epidermal Homeostasismentioning

confidence: 99%

Mammalian Epidermis: A Compendium of Lipid Functionality

Rudan

Watt

2022

Front. Physiol.

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“…Over the past years, several studies have reported an increase in the expression of sphingomyelin deacylase and a reduction in the expression of sphingomyelinase (SMase) in AD, which may cause a decrease in total ceramides (72). In relation to this, mice lacking the enzyme ceramide synthase 4 (CERS4) present a disrupted epidermis and a CD45infiltrated dermis, even without the topical application of an allergen or irritant (73). In contrast, high levels of CERS4 in AD contribute to the enhanced synthesis of short-chain ceramides (74), constructing a healthier skin, more resistant to aggressions.…”

Section: Sphingolipid and Atopic Dermatitismentioning

confidence: 99%

The Role of Sphingolipids in Allergic Disorders

et al. 2021

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Allergy is defined as a complex chronic inflammatory condition in which genetic and environmental factors are implicated. Sphingolipids are involved in multiple biological functions, from cell membrane components to critical signaling molecules. To date, sphingolipids have been studied in different human pathologies such as neurological disorders, cancer, autoimmunity, and infections. Sphingolipid metabolites, in particular, ceramide and sphingosine-1-phosphate (S1P), regulate a diverse range of cellular processes that are important in immunity and inflammation. Moreover, variations in the sphingolipid concentrations have been strongly associated with allergic diseases. This review will focus on the role of sphingolipids in the development of allergic sensitization and allergic inflammation through the activation of immune cells resident in tissues, as well as their role in barrier remodeling and anaphylaxis. The knowledge gained in this emerging field will help to develop new therapeutic options for allergic disorders.

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“…In the end, N-acylation of sphinganine by CerS1-S6, produces dihydroceramide which is afterwards converted into ceramide via dihydroceramide desaturase 1 (Des1) [15]. Therefore, ceramides are synthesized by a family of six CerS, each isoform displaying specificities for the chain length of the added acyl-CoA [16][17][18][19][20][21][22][23][24][25][26][27], and possess different properties depending on their chain length (Table 1). May serve as biomarkers in determining the effectiveness of anticancer agents; C16:0 is a significant factor in the development of obesity and its related complications.…”

Section: Ceramidesmentioning

confidence: 99%

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (ATS) are worldwide known diseases with increased incidence and prevalence. These two are driven and are interconnected by multiple oxidative and metabolic functions such as lipotoxicity. A gamut of evidence suggests that sphingolipids (SL), such as ceramides, account for much of the tissue damage. Although in humans they are proving to be accurate biomarkers of adverse cardiovascular disease outcomes and NAFLD progression, in rodents, pharmacological inhibition or depletion of enzymes driving de novo ceramide synthesis prevents the development of metabolic driven diseases such as diabetes, ATS, and hepatic steatosis. In this narrative review, we discuss the pathways which generate the ceramide synthesis, the potential use of circulating ceramides as novel biomarkers in the development and progression of ATS and related diseases, and their potential use as therapeutic targets in NAFDL-ATS development which can further provide new clues in this field.

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Murine Epidermal Ceramide Synthase 4 Is a Key Regulator of Skin Barrier Homeostasis

Cited by 12 publications

References 46 publications

Mammalian Epidermis: A Compendium of Lipid Functionality

Mammalian Epidermis: A Compendium of Lipid Functionality

The Role of Sphingolipids in Allergic Disorders

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

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