Various peroxisome proliferator-activated receptor (PPAR)-γagonists differently induce differentiation of cultured human keratinocytes

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Abstract

Peroxisome proliferator-activated receptors (PPARs) are potentially useful for the treatment of skin diseases, because they stimulate keratinocyte differentiation, exert anti-inflammatory effects and improve barrier function. We examined five PPAR-γ agonists, including four thiazolidinediones (ciglitazone, troglitazone, rosiglitazone and pioglitazone) and an angiotensin-II receptor blocker (telmisartan), for their ability to upregulate filaggrin and loricrin expression at both mRNA and protein levels in cultured normal human keratinocytes (NHKs). Troglitazone, rosiglitazone, pioglitazone and telmisartan significantly increased filaggrin expression at both mRNA and protein levels in calcium-induced differentiated NHKs. Rosiglitazone and pioglitazone, but not troglitazone nor telmisartan, also significantly increased loricrin expression at both mRNA and protein levels in differentiated NHKs. These effects were not found in undifferentiated NHKs nor differentiated NHKs treated with ciglitazone. This study revealed differential effects of various PPAR-γ agonists on epidermal differentiation, and the most potent of those are rosiglitazone and pioglitazone.

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