Title:The Epigenetic Contribution to the Pathogenesis of Psoriasis: Recent
Advances
Volume: 31
Issue: 29
关键词:
牛皮癣，自身免疫，表观遗传学，DNA甲基化，组蛋白修饰，非编码RNA。
摘要: Psoriasis is defined as a chronic autoimmune disorder of the skin in which abnormal proliferation
and differentiation of keratinocytes are blamed as the central culprit of disease etiopathogenesis.
A complex interplay between environmental factors and genetic risk factors has been
suggested to trigger the disease. However, epigenetic regulation appears to connect external stimuli
and genetic abnormalities in the development of psoriasis. The discordance in the prevalence of
psoriasis between monozygotic twins and environmental factors that contribute to its onset have
caused a paradigm shift regarding the mechanisms underlying the pathogenesis of this disease. Epigenetic
dysregulation may be involved in aberrancies of keratinocyte differentiation, T-cell activation,
and other plausible cells, leading to the initiation and perpetuation of psoriasis. Epigenetics is
characterized by heritable alterations in the transcription of genes without nucleotide change and is
commonly considered at three levels, i.e., DNA methylation, histone modifications, and microRNAs.
To date, scientific evidence has indicated abnormal DNA methylation, histone modifications,
and non-coding RNA transcription in psoriatic patients. In order to reverse aberrant epigenetic
changes in psoriasis patients, several compounds and drugs (epi-drugs) have been developed to affect
the major enzymes involved in the methylation of DNA, or the acetylation of histones, which
aim to correct the aberrant methylation and acetylation patterns. A number of clinical trials have
suggested the therapeutic potential of such drugs in the treatment of psoriasis. In the present review,
we attempt to clarify recent findings with respect to epigenetic irregularities in psoriasis and
discuss future challenges.
