Skin inflammation and impaired adipogenesis in a mouse model of acid ceramidase deficiency. J Inherit Metab Dis 2022 Nov;45(6):1175-1190
Date
09/10/2022Pubmed ID
36083604Pubmed Central ID
PMC9826362DOI
10.1002/jimd.12552Scopus ID
2-s2.0-85138302520 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
Acid ceramidase catalyzes the degradation of ceramide into sphingosine and a free fatty acid. Acid ceramidase deficiency results in lipid accumulation in many tissues and leads to the development of Farber disease (FD). Typical manifestations of classical FD include formation of subcutaneous nodules and joint contractures as well as the development of a hoarse voice. Healthy skin depends on a unique lipid profile to form a barrier that confers protection from pathogens, prevents excessive water loss, and mediates cell-cell communication. Ceramides comprise ~50% of total epidermis lipids and regulate cutaneous homeostasis and inflammation. Abnormal skin development including visual skin lesions has been reported in FD patients, but a detailed study of FD skin has not been performed. We conducted a pathophysiological study of the skin in our mouse model of FD. We observed altered lipid composition in FD skin dominated by accumulation of all studied ceramide species and buildup of abnormal storage structures affecting mainly the dermis. A deficiency of acid ceramidase activity also led to the activation of inflammatory IL-6/JAK/signal transducer and activator of transcription 3 and noncanonical NF-κB signaling pathways. Last, we report reduced proliferation of FD mouse fibroblasts and adipose-derived stem/stromal cells (ASC) along with impaired differentiation of ASCs into mature adipocytes.
Author List
Rybova J, Kuchar L, Sikora J, McKillop WM, Medin JAAuthor
Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Acid CeramidaseAdipogenesis
Animals
Ceramides
Disease Models, Animal
Farber Lipogranulomatosis
Inflammation
Mice