Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Clinical Research Center for Cancer Immunotherapy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Published: September 2023
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Article Abstract
Psoriasis is a common and recurrent inflammatory skin disease characterized by inflammatory cells infiltration of the dermis and excessive proliferation, reduced apoptosis, and abnormal keratosis of the epidermis. In this study, we found that G9A, an important methyltransferase that mainly mediates the mono-methylation (me1) and di-methylation (me2) of histone 3 lysine 9 (H3K9), is highly expressed in lesions of patients with psoriasis and imiquimod (IMQ)-induced psoriasis-like mouse model. Previous studies have shown that G9A is involved in the pathogenesis of various tumors by regulating apoptosis, proliferation, differentiation, and invasion. However, the role of G9A in skin inflammatory diseases such as psoriasis remains unclear. Our data so far suggest that topical administration of G9A inhibitor BIX01294 as well as keratinocyte-specific deletion of G9A greatly alleviated IMQ-induced psoriatic alterations in mice for the first time. Mechanistically, the loss function of G9A causes the downregulation of Ectodysplasin A receptor (EDAR), consequently inhibiting the activation of NF-κB pathway, resulting in impaired proliferation and increased apoptosis of keratinocytes, therefore ameliorating the psoriatic dermatitis induced by IMQ. In total, we show that inhibition of G9A improves psoriatic-like dermatitis mainly by regulating cell proliferation and apoptosis rather than inflammatory processes, and that this molecule may be considered as a potential therapeutic target for keratinocyte hyperproliferative diseases such as psoriasis.
Psoriasis is an autoimmune skin disease, and Boswellia serrata (BS) gum resin shows potential in managing inflammatory conditions, although its effectiveness is limited due to poor absorption in the body.
The study tests a new formulation of Boswellia called Boswellia nano emulsion gel (BNG) on mice with dermatitis induced to resemble psoriasis, finding that BNG significantly reduces inflammation and the associated symptoms.
Results indicated that treatment with BNG lowers gene expression linked to inflammation compared to control groups, suggesting its therapeutic potential, but more clinical studies are needed to confirm these findings in humans.
A 69-year-old man with severe atopic dermatitis (AD) received a single 600 mg subcutaneous injection of dupilumab, which resulted in a psoriatic rash on day 10. He was then given 30 mg of oral upadacitinib daily, and after 10 weeks of treatment, both the AD and the psoriasis had significantly improved. However, at week 16, the patient had no bowel movement for a week, and paralytic ileus was suspected based on the patient's symptoms and laboratory findings.
School of Biological Sciences, Faculty of Biology Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PT, UK.
Psoriasis (Ps) is a debilitating immune-mediated chronic skin condition. It affects about 1-3% of the world population, with an 8-11% prevalence in Northern European populations. Tyrosine kinase 2 (TYK2) is a newly identified target for Ps.
Bergapten (BP) is a plant-derived furocoumarin that has a wide range of pharmacological effects. BP serves as a candidate amplifier in phototherapy against skin inflammation, such as psoriasis and atopic dermatitis. However, the anti-inflammatory role of BP remains elusive.
