Abstract
BackgroundPsoriasis is a common chronic inflammatory skin disease that features the abnormal proliferation of keratinocytes. This proliferation could partly result from disturbances in vitamin A metabolism. Changes in psoriasis patients of the levels of retinol-binding protein 4 (RBP4), a carrier of retinol (vitamin A); transmembrane protein stimulated by retinoic acid 6 (STRA6); and other retinol metabolic molecules have not yet been fully established. Therefore, we investigated vitamin A-related proteins in mice with imiquimod (IMQ)-induced psoriasis.MethodsThirty mice were divided into four study groups: two groups underwent IMQ application for 3 or 6 days (groups A and B, respectively), and two groups underwent Vaseline application for 3 or 6 days (groups C and D, respectively). Blood and skin samples from both lesional and non-lesional areas of the mice were analyzed using enzyme-linked immunosorbent assays, hematoxylin and eosin staining, immunochemistry, real-time reverse transcription polymerase chain reaction, and RNA sequencing.ResultsIMQ-treated mice developed erythema, scales, and skin thickening. Compared with the control groups, IMQ-treated groups had the following changes: 1) interleukin (IL)-17A, IL-23, and tumor necrosis factor (TNF)-α levels were raised significantly in both serum and lesional skin (all p < 0.001); 2) retinol levels in lesional skin increased slightly (p = 0.364), but no change was evident in serum retinol levels; 3) STRA6 was upregulated in both lesional skin (p = 0.021) and serum (p = 0.034); 4) RBP4 levels were elevated in serum (p = 0.042), but exhibited only an increasing trend (p = 0.273) in lesional skin; and 5) proteins and enzymes that mediate retinoic acid formation and transformation were upregulated in lesional skin.ConclusionsAs the demand for vitamin A in psoriatic mice increased, retinol underwent relocation from the circulation to target tissues. RBP4, STRA6, and the transformation from retinol to retinoic acid were upregulated, which may be part of the mechanism of psoriasis skin lesion formation. We propose that a positive feedback mechanism was formed that maintained the severity of psoriasis.
Highlights
Psoriasis is a T-cell-mediated, genetically determined, environmentally influenced, chronic inflammatory skin condition that affects almost 2–3% of the population [1]
Various proteins are involved in retinol metabolism, including cellular retinol binding protein 1 and 2 (CRBP1 and 2), cellular retinoic acid binding protein 1 and 2 (CRABP1 and 2), lecithin retinol acyltransferase (LRAT), retinal dehydrogenases (RDH), and members of the cytochrome P450 family (CYP2, 3, and 4) [5]
The aims of the present study were to create a psoriasis mouse model and to use it to detect the levels of retinol-binding protein 4 (RBP4), stimulated by retinoic acid 6 (STRA6), retinol, and other vitamin A-related molecules in the circulation and in skin lesions
Summary
Psoriasis is a T-cell-mediated, genetically determined, environmentally influenced, chronic inflammatory skin condition that affects almost 2–3% of the population [1]. Retinol combines with RBP4 to form a complex (holo-RBP4) When this complex reaches a target tissue, it interacts with a specific membrane protein called stimulated by retinoic acid 6 (STRA6), and the RBP4 comes back into the circulation as apo-RBP4. STRA6 is a transmembrane protein with unique structural characteristics that can catalyze bidirectional retinol transportation and sequester retinol into target cells. It functions as a cytokine receptor that activates and programs several signaling pathways that drive proliferation and differentiation of human skin cells [8, 9]. After retinol is transported into target cells, it is metabolized into retinal and retinoic acid (RA), which further activates downstream signaling pathways that regulate skin proliferation. We investigated vitamin A-related proteins in mice with imiquimod (IMQ)-induced psoriasis
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