title: 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.
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan; Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Minao
authors.initials: M
authors.lastname: Furumura
authors.forename: Sanae
authors.initials: S
authors.lastname: Numata
authors.forename: Kwesi
authors.initials: K
authors.lastname: Teye
authors.forename: Tadashi
authors.initials: T
authors.lastname: Karashima
authors.forename: Bungo
authors.initials: B
authors.lastname: Ohyama
authors.forename: Norifumi
authors.initials: N
authors.lastname: Tanida
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001562:Benzimidazoles / Q000737:chemistry; D001565:Benzoates / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000737:chemistry; D000091344:Filaggrin Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D008565:Membrane Proteins / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D000077154:Rosiglitazone; D012867:Skin / Q000187:drug effects; D000077333:Telmisartan; D045162:Thiazolidinediones / Q000737:chemistry*; D000077288:Troglitazone
chemical_list: D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D001565:Benzoates; D002839:Chromans; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; C064554:loricrin; D000077154:Rosiglitazone; C089946:2,4-thiazolidinedione; D000077288:Troglitazone; D000077333:Telmisartan; C039671:ciglitazone; D000077205:Pioglitazone
keywords: filaggrin; keratinocyte; loricrin; peroxisome proliferator-activated receptors; thiazolidinedione