Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model

Abstract Background Psoriasis 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...

Full description

Bibliographic Details
Main Authors: Hai-meng Wang, Chao Wu, Yan-yun Jiang, Wen-ming Wang, Hong-zhong Jin
Format: Article
Language:English
Published: BMC 2020-01-01
Series:Nutrition & Metabolism
Subjects:
Online Access:https://doi.org/10.1186/s12986-019-0423-y
_version_ 1811270921405595648
author Hai-meng Wang
Chao Wu
Yan-yun Jiang
Wen-ming Wang
Hong-zhong Jin
author_facet Hai-meng Wang
Chao Wu
Yan-yun Jiang
Wen-ming Wang
Hong-zhong Jin
author_sort Hai-meng Wang
collection DOAJ
description Abstract Background Psoriasis 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. Methods Thirty 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. Results IMQ-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. Conclusions As 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.
first_indexed 2024-04-12T22:11:56Z
format Article
id doaj.art-6f764000343648ddb20177c7f4a72b4a
institution Directory Open Access Journal
issn 1743-7075
language English
last_indexed 2024-04-12T22:11:56Z
publishDate 2020-01-01
publisher BMC
record_format Article
series Nutrition & Metabolism
spelling doaj.art-6f764000343648ddb20177c7f4a72b4a2022-12-22T03:14:43ZengBMCNutrition & Metabolism1743-70752020-01-0117111510.1186/s12986-019-0423-yRetinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine modelHai-meng Wang0Chao Wu1Yan-yun Jiang2Wen-ming Wang3Hong-zhong Jin4Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Skin and Immune DiseasesDepartment of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Skin and Immune DiseasesDepartment of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Skin and Immune DiseasesDepartment of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Skin and Immune DiseasesDepartment of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Skin and Immune DiseasesAbstract Background Psoriasis 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. Methods Thirty 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. Results IMQ-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. Conclusions As 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.https://doi.org/10.1186/s12986-019-0423-yPsoriasisMouseRetinolRBP4STRA6
spellingShingle Hai-meng Wang
Chao Wu
Yan-yun Jiang
Wen-ming Wang
Hong-zhong Jin
Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model
Nutrition & Metabolism
Psoriasis
Mouse
Retinol
RBP4
STRA6
title Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model
title_full Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model
title_fullStr Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model
title_full_unstemmed Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model
title_short Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model
title_sort retinol and vitamin a metabolites accumulate through rbp4 and stra6 changes in a psoriasis murine model
topic Psoriasis
Mouse
Retinol
RBP4
STRA6
url https://doi.org/10.1186/s12986-019-0423-y
work_keys_str_mv AT haimengwang retinolandvitaminametabolitesaccumulatethroughrbp4andstra6changesinapsoriasismurinemodel
AT chaowu retinolandvitaminametabolitesaccumulatethroughrbp4andstra6changesinapsoriasismurinemodel
AT yanyunjiang retinolandvitaminametabolitesaccumulatethroughrbp4andstra6changesinapsoriasismurinemodel
AT wenmingwang retinolandvitaminametabolitesaccumulatethroughrbp4andstra6changesinapsoriasismurinemodel
AT hongzhongjin retinolandvitaminametabolitesaccumulatethroughrbp4andstra6changesinapsoriasismurinemodel