Various peroxisome proliferator‐activated receptor (PPAR)‐γ agonists differently induce differentiation of cultured human keratinocytes

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.

Inhibition of tumorigenesis by peroxisome proliferator-activated receptor (PPAR)-dependent cell cycle blocks in human skin carcinoma cells

“…The latter is mediated via shuttling of PPARβ/δ into the nucleus with other proteins that in turn modulates E2F signaling (Zhu et al 2012). Alternatively, there is also evidence that PPARβ/δ and PPARγ ligands can induce terminal differentiation, which is known to cause inhibition of the cell cycle consistent with that observed in these studies (Demerjian et al 2006; Mao-Qiang et al 2004; Schmuth et al 2004; Westergaard et al 2001; Yan et al 2015). While ligand activation of PPARβ/δ and PPARγ caused modulation of cell cycle and proliferation, only expression of PPARβ/δ and PPARγ was required for inhibition of tumorigenicity.…”

Effects of <i>Asterias amurensis</i>-derived Sphingoid Bases on the <i>de novo</i> Ceramide Synthesis in Cultured Normal Human Epidermal Keratinocytes

“…Bases such as d18:3 and 9-Med18:3 also bear a C8 double bond, indicating that ASBs may activate PPARs and induce ceramide production through a similar process. PPARγ agonists strongly stimulate filaggrin and loricrin gene expressions but only enhance their corresponding protein levels during the NHEK differentiation stage 39 . Therefore, sphingolipid production obeys different mechanisms depending on the NHEK differentiation.…”

Treatment with Docosahexaenoic Acid Improves Epidermal Keratinocyte Differentiation and Ameliorates Inflammation in Human Keratinocytes and Reconstructed Human Epidermis Models

“…All epidermal layers contain PPARβ/δ, but PPARα and PPARγ are present in the epidermal suprabasal layer. Qiang [23] and Yan [24] have demonstrated that PPARγ agonists can stimulate cultured human keratinocyte differentiation and repair the skin barrier in mouse models. Meanwhile, a PPAR-α agonist like WY14643 increases the expression of some epidermal differentiation structural proteins, which may be critical in human keratinocyte differentiation.…”