title: Psoriasis Skin Inflammation-Induced microRNA-26b Targets NCEH1 in Underlying Subcutaneous Adipose Tissue.
abstract: Psoriasis is an immune-mediated inflammatory disease, which is associated with a high risk of developing systemic comorbidities, such as obesity, cardiovascular disease, and diabetes mellitus. However, the mechanistic links between psoriatic skin inflammation and systemic comorbidities remain largely unknown. MicroRNAs (miRNAs) are recently discovered gene regulators that play important roles in psoriasis skin inflammation. In this study we aimed to explore whether the skin inflammation in psoriasis affects miRNA expression of the underlying subcutaneous adipose tissue and whether this may be a link between psoriasis and comorbidities. To this end, we compared the miRNA expression profile of subcutaneous adipose tissue underneath lesional and nonlesional psoriatic skin. We further validated the differential expression of several miRNAs and characterized their expression patterns in different cell types present in subcutaneous adipose tissue. We focused on miR-26b-5p, which was highly up-regulated in subcutaneous adipose tissue underneath lesional psoriasis skin. We showed that it targets and down-regulates neutral cholesterol ester hydrolase 1, an enzyme essential for cholesterol efflux, in monocytes/macrophages, adipocytes, vascular endothelial cells, and fibroblasts. We conclude that this miRNA may serve as a mechanistic link between psoriatic skin inflammation and its systemic comorbidities.
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Louisa
authors.initials: L
authors.lastname: Cheung
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Fisher
authors.affiliation: Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Natalia
authors.initials: N
authors.lastname: Kuzmina
authors.affiliation: Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Li
authors.affiliation: Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Olivera
authors.initials: O
authors.lastname: Werngren
authors.affiliation: Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Blomqvist
authors.affiliation: Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: mona.stahle@ki.se.
authors.forename: Mona
authors.initials: M
authors.lastname: Ståhle
authors.affiliation: Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: ning.xu@ki.se.
authors.forename: Ning Xu
authors.initials: NX
authors.lastname: Landén
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis / Q000453:epidemiology; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D012494:Sampling Studies; D002787:Sterol Esterase; D050151:Subcutaneous Fat / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D002265:Carboxylic Ester Hydrolases; C515677:NCEH1 protein, human; D002787:Sterol Esterase