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.

Psoriasis and comorbid diseases

“…Additionally, persistent pathophysiologic processes that drive psoriasis (e.g., epidermal hyper-proliferation, inflammation, 49,50 and angiogenesis) may also exert pleiotropic adverse effects on the CV system that contribute to atherogenesis. Mouse models of psoriasis have demonstrated that chronic skin-specific inflammation has systemic effects including arterial hypertension 51 , endothelial dysfunction 51 , and vascular inflammation and thrombosis.…”

MiR‐126 correlates with increased disease severity and promotes keratinocytes proliferation and inflammation while suppresses cells' apoptosis in psoriasis

“…MicroRNAs (miRNAs) are a class of small noncoding RNAs that play crucial roles in the regulation of biological processes in signal transduction, cells' proliferation, differentiation, and apoptosis . Accumulating studies disclose that dysregulation of miRNAs including miR‐31, miR‐155, and miR‐26b is involved in the pathological processes of a variety of immune diseases including psoriasis . MiR‐126, located on human chromosome 9q34.3, has been reported to participate in the development and progression of multiple immune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD) .…”

“…[9][10][11][12] Accumulating studies disclose that dysregulation of miRNAs including miR-31, miR-155, and miR-26b is involved in the pathological processes of a variety of immune diseases including psoriasis. [13][14][15] MiR-126, located on human chromosome 9q34.3, has been reported to participate in the development and progression of multiple immune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). [16][17][18] However, to the best of our knowledge, the role of miR-126 in the etiology of psoriasis has not been reported.…”

Biological links in periodontitis and rheumatoid arthritis: Discovery via text‐mining PubMed abstracts

“…Hsa‐mir‐17‐5p is linked to autoimmune disease, and is upregulated in multiple sclerosis affected T‐helper cells . miRNA 26 are systemically elevated in RA, while hsa‐mir‐26b‐5p, in particular is implicated in autoimmune psoriasis . Hsa‐mir‐16‐5p regulates immune, apoptosis and epithelial barrier functions, and is an emerging biomarker of early disease and therapeutic response in RA .…”

“…are systemically elevated in RA, 72 while hsa-mir-26b-5p, in particular is implicated in autoimmune psoriasis. 73 Hsa-mir-16-5p regulates immune, apoptosis and epithelial barrier functions, and is an emerging biomarker of early disease and therapeutic response in RA. 74,75 It is also upregulated in periodontitis.…”