Abnormal expression of SIRTs in psoriasis: Decreased expression of SIRT 1-5 and increased expression of SIRT 6 and 7

Fan,Xiaojing; Yan,Kexiang; Meng,Qinqin; Sun,Rui; Yang,Xinrong; Yuan,Dingfen; Li,Fulun; Deng,Hui

doi:10.3892/ijmm.2019.4173

Abnormal expression of SIRTs in psoriasis: Decreased expression of SIRT 1-5 and increased expression of SIRT 6 and 7

Authors:
- Xiaojing Fan
- Kexiang Yan
- Qinqin Meng
- Rui Sun
- Xinrong Yang
- Dingfen Yuan
- Fulun Li
- Hui Deng
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Affiliations: Department of Dermatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China, Shanghai Institute of Dermatology and Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China , Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China, Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China
Published online on: April 24, 2019 https://doi.org/10.3892/ijmm.2019.4173
Pages: 157-171
Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The prevalence of psoriasis is increasing, and poses a serious risk to human health and quality of life. Psoriasis, a chronic immune‑mediated skin disease with epidermal hyperkeratosis and parakeratosis, is associated with numerous complications, including metabolic syndromes that are regulated by sirtuins (SIRTs) via deacetylation. As they serve a necessary function in inflammation and metabolism, SIRTs are considered to link inflammation and metabolic syndrome. Previous studies have indicated that SIRTs serve a function in the pathophysiology of psoriasis, but to date no detailed research has been conducted investigating the expression levels and patterns of SIRTs in psoriasis. The present study investigated the abnormal expression of SIRTs in psoriasis and provided a theoretical foundation for the treatment and prognosis of psoriasis. Tumor necrosis factor (TNF)‑α‑stimulated HaCaT cells and an imiquimod‑induced psoriasis mouse model were used to produce in vitro and in vivo models, respectively. Psoriasis clinical specimens (psoriasis area and severity index >10; n=22) and normal group specimens (n=22) were obtained from human subjects. The mRNA and protein expression levels in human and mouse skin lesions and TNF‑α‑stimulated HaCaT cells were detected using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting, and compared with the control groups. The expression patterns of SIRT proteins were investigated using immunofluorescence (IF) staining. The expression levels of SIRT1, SIRT2, SIRT3, SIRT4 and SIRT5 were downregulated while those of SIRT6 and SIRT7 were upregulated in skin lesions and TNF‑α‑stimulated HaCaT cells compared with the control group as determined by RT‑qPCR, western blotting and IF. Statistically significant differences were observed in vivo and in vitro. P‑values of SIRT1‑7 mRNA are less than 0.05 in RT‑qPCR, and the P‑values of SIRT1‑7 proteins are less than 0.05 except for SIRT4 in the western blot analysis. SIRTs serve notable functions in severe psoriasis dermatitis, with the overexpression of SIRT6 and SIRT7 potentially induced by the adaptive immune response, and the downregulation of SIRT1, SIRT2, SIRT3, SIRT4 and SIRT5 may be a result of an internal environment imbalance in vivo. Psoriasis is an inflammation and metabolism‑associated disease mediated by the SIRT family. The present results provide a novel potential mechanism and strategy for the treatment of psoriasis by modulating the function and expression of SIRTs.

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