HDAC inhibitors are a promising therapy for psoriasis


According to a study appearing in the journal Investigative Dermatology, a powerful class of cancer drugs -- HDAC inhibitors -- might also be used to treat psoriasis.

Psoriasis is a common, long-lasting skin disease affecting 1-3 percent of the population. The disease is characterized by red, scaly, raised plaques at different body sites. Psoriasis is considered an autoimmune disease but its mechanistic underpinnings are yet to be defined.

Previous studies have demonstrated that Aquaporin-3 (AQP3), a water and glycerol channel, is implicated in the proliferation, differentiation, and migration of skin cells, skin hydration, and wound healing. AQP3 is one of the several aquaporins that are expressed in mammalian skin, and it helps transport water and glycerol, both of which are known to influence skin tissue. Decreased expression of AQP3 was identified in psoriasis-affected skin, compared to a healthy control. This highlights that abnormal AQP3 function may be a feature of psoriasis.

Speculation has risen that histone deacetylase (HDAC) inhibitors may have therapeutic effects on skin disorders. In this study, researchers from Augusta University and Charlie Norwood VA Medical Center sought to determine how HDAC affects AQP3. They tested a broad-spectrum HDAC inhibitor called SAHA in keratinocytes, the predominant cells in the skin epidermis. Results showed that SAHA caused normal keratinocytes to express higher levels of AQP3, which in turn enhanced glycerol uptake in these cells.

Further experiments demonstrated a role of HDAC3 in suppressing AQP3 expression. In addition, the protein p53 is implicated in regulating HDAC inhibitor-induced AQP3 expression. Collectively, the study demonstrates for the first time that the expression of AQP3 in skin cells is modulated by both HDAC3 and p53.

The HDAC inhibitor SAHA has already been approved by the FDA for the treatment of cutaneous T-cell lymphoma. This study indicates that administration of SAHA may be a new approach to treating psoriasis and other skin disorders that involve abnormal AQP3 function.
 
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