title: Phosphatidic acid has a potential to promote hair growth in vitro and in vivo, and activates mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in hair epithelial cells.
abstract: Phospholipids have recently been discovered to play an important role in cellular regulation. In this study, we focused on phosphatidic acid and lysophosphatidic acid, which are phospholipids known to possess growth-hormonal effects on several types of cells, and examined their growth-promoting effects on murine hair epithelial cells. We discovered that phosphatidic acid possesses intensive growth-promotional effects on hair epithelial cells and epidermal keratinocytes. In contrast, lyso-phosphatidic acid showed lower growth-promoting effects on hair epithelial cells relative to phosphatidic acid and showed minimal or no growth-promoting activity on epidermal keratinocytes. Phosphatidic acid was also shown to have hair-growing activity to induce the anagen phase of the hair cycle in the in vivo murine model. For the purpose of examining the hair-growing mechanisms of phosphatidic acid, we examined its relationship to the mitogen-activated protein kinase cascade linked to cell proliferation and the transforming growth factor beta signal pathway known to be a regulator of catagen induction. We confirmed that phosphatidic acid activates MEK-1/2 and upregulates the expression of MEK-1/2 in cultured murine hair epithelial cells. Addition of transforming growth factor beta1 to hair epithelial cell cultures concentration-dependently decreased cell growth and induced apoptosis; however, addition of phosphatidic acid to the culture neutralized the growth-inhibiting effects of transforming growth factor beta1 and protected the cells from apoptosis. We speculate that the hair-growing activity of phosphatidic acid is at least linked to its growth-promoting effects on hair epithelial cells that follow mitogen-activated protein kinase/extracellular signal-regulated kinase kinase activation and its protective action on transforming-growth-factor-beta1-induced apoptosis that is assumed to trigger catagen induction in the hair cycle.
authors.affiliation: Tsukuba Research Laboratories, Kyowa Hakko Kogyo Company, 2 Miyukigaoka, Tsukuba, Ibaraki 305-0841, Japan. tomoya-goma@mx6.ttcn.ne.jp
authors.forename: Tomoya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Ayako
authors.initials: A
authors.lastname: Kamimura
authors.forename: Takako
authors.initials: T
authors.lastname: Hamazono-Matsuoka
authors.forename: Shinkichi
authors.initials: S
authors.lastname: Honda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D006197:Hair / Q000187:drug effects* / Q000254:growth & development*; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008246:Lysophospholipids / Q000494:pharmacology*; D048370:MAP Kinase Kinase 2; D048728:MAP Kinase Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010712:Phosphatidic Acids / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: D008246:Lysophospholipids; D010712:Phosphatidic Acids; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C037657:dioleoylphosphatidic acid; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D048728:MAP Kinase Kinase Kinase 1; C482578:Map3k1 protein, mouse; D048370:MAP Kinase Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases