1. Hypotonic, acidic oxidizing solution containing hypochlorous acid (HClO) as a potential treatment of hailey-hailey disease
- Author
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Azzurra Zonfrilli, Matteo Franchitto, Claudio Talora, Salvatore Calabro, Samantha Cialfi, and Isabella Screpanti
- Subjects
keratinocytes ,Pemphigus, Benign Familial ,Hypochlorous acid ,NF-E2-Related Factor 2 ,Pharmaceutical Science ,Calcium-Transporting ATPases ,medicine.disease_cause ,hailey-hailey disease ,oxidative-stress ,Article ,Antioxidants ,Cell Line ,Analytical Chemistry ,030207 dermatology & venereal diseases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,Drug Discovery ,medicine ,Humans ,Physical and Theoretical Chemistry ,030304 developmental biology ,Wound Healing ,0303 health sciences ,Organic Chemistry ,medicine.disease ,Hailey–Hailey disease ,In vitro ,Hypochlorous Acid ,Solutions ,Oxidative Stress ,Gene Expression Regulation ,Hypotonic Solutions ,chemistry ,Chemistry (miscellaneous) ,Cancer research ,Cytokines ,Molecular Medicine ,Recurrent skin infections ,Reactive Oxygen Species ,Wound healing ,Acids ,Oxidation-Reduction ,Oxidative stress - Abstract
Hailey&ndash, Hailey disease (HHD) is a rare, chronic and recurrent blistering disorder, characterized by erosions occurring primarily in intertriginous regions and histologically by suprabasal acantholysis. Mutation of the Golgi Ca2+-ATPase ATP2C1 has been identified as having a causative role in Hailey&ndash, Hailey disease. HHD-derived keratinocytes have increased oxidative-stress that is associated with impaired proliferation and differentiation. Additionally, HHD is characterized by skin lesions that do not heal and by recurrent skin infections, indicating that HHD keratinocytes might not respond well to challenges such as wounding or infection. Hypochlorous acid has been demonstrated in vitro and in vivo to possess properties that rescue both oxidative stress and altered wound repair process. Thus, we investigated the potential effects of a stabilized form of hypochlorous acid (APR-TD012) in an in vitro model of HHD. We found that treatment of ATP2C1-defective keratinocytes with APR-TD012 contributed to upregulation of Nrf2 (nuclear factor (erythroid-derived 2)-like 2). Additionally, APR TD012-treatment restored the defective proliferative capability of siATP2C1-treated keratinocytes. We also found that the APR-TD012 treatment might support wound healing process, due to its ability to modulate the expression of wound healing associated cytokines. These observations suggested that the APR-TD012 might be a potential therapeutic agent for HHD-lesions.
- Published
- 2019