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Published on: May 4, 2021
Psoriasis Skin Inflammation-Induced microRNA-26b Targets NCEH1 in Underlying Subcutaneous Adipose Tissue
Louisa Cheung1, Rachel M Fisher1, Natalia Kuzmina2
1Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
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.
Insights
Psoriasis skin inflammation alters microRNA (miRNA) expression in nearby fat tissue. This change, particularly miR-26b-5p, may mechanistically link psoriasis to systemic conditions like cardiovascular disease.
Area of Science:
- Immunodermatology
- Molecular Biology
- Metabolic Disease Research
Background:
- Psoriasis is an immune-mediated inflammatory disease.
- Psoriasis is linked to systemic comorbidities like obesity, cardiovascular disease, and diabetes mellitus.
- The mechanistic links between psoriatic skin inflammation and systemic comorbidities are not well understood.
Purpose of the Study:
- To investigate if skin inflammation in psoriasis affects microRNA (miRNA) expression in subcutaneous adipose tissue.
- To explore if altered miRNA expression in adipose tissue serves as a link between psoriasis and its comorbidities.
Main Methods:
- Comparison of miRNA expression profiles in subcutaneous adipose tissue from lesional and nonlesional psoriatic skin.
- Validation of differentially expressed miRNAs.
- Characterization of miRNA expression patterns in various cell types within subcutaneous adipose tissue.
- Focus on miR-26b-5p and its target, neutral cholesterol ester hydrolase 1 (NCEH1).
Main Results:
- Significant differences in miRNA expression were observed in subcutaneous adipose tissue beneath lesional psoriatic skin compared to nonlesional skin.
- miR-26b-5p was highly upregulated in adipose tissue under lesional psoriatic skin.
- miR-26b-5p was found to target and downregulate NCEH1 in multiple cell types including monocytes/macrophages, adipocytes, vascular endothelial cells, and fibroblasts.
Conclusions:
- Skin inflammation in psoriasis impacts miRNA expression in the underlying subcutaneous adipose tissue.
- Upregulated miR-26b-5p in adipose tissue may represent a mechanistic link between psoriatic skin inflammation and systemic comorbidities.
- Targeting miR-26b-5p or its downstream effects could offer therapeutic strategies for managing psoriasis-associated systemic conditions.
