Molecular pharmacological analysis of skin barrier regulatory mechanisms
Description: The skin barrier protects the body from water loss, allergens and pathogens. In this study, we used cultured normal human epidermal keratinocytes, and screened compounds for promotion of skin barrier with induction of a skin barrier protein, filaggrin (FLG) as a parameter. We then extended these in vitro findings to in vivo models. We found, ① lysophosphatidic acid (LPA) acts on its receptors, LPAR1 and LPAR5, to mobilize G12/13-Rho-ROCK-SRF pathway, and promote skin barrier function through keratinocyte maturation, and ② LPA, in addition, induces differentiation of keratinocyte into a separate population involved in skin wound healing. We further found, ③ a class of compounds that induce keratinocyte maturation for barrier function through acting aryl hydrocarbon receptor (AhR), but, unlike conventional AhR ligands such as FICZ and TCDD, are weak or negligible in classic AhR ligand activity such as CYP1A1 induction and apparently without proinflammatory activity.
Amount: ¥41,730,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (A)
Start date: 2017-04-01
End date: 2020-03-31
Investigator: shuh narumiya
Institution: Kyoto University
Funded outputs count: 15
Funder award ID: 17H01531
OpenAlex ID: G3552604366