title: PPARgamma activators stimulate aquaporin 3 expression in keratinocytes/epidermis.
abstract: Aquaporin 3 (AQP3), a member of the aquaglyceroporin family, which transports water and glycerol, is robustly expressed in epidermis and plays an important role in stratum corneum hydration, permeability barrier function and wound healing. PPAR and LXR activation regulates the expression of many proteins in the epidermis and thereby can affect epidermal function. Here, we report that PPARgamma activators markedly stimulate AQP3 mRNA expression in both undifferentiated and differentiated cultured human keratinocytes (CHKs). The increase in AQP3 mRNA by PPARgamma activator occurs in a dose- and time-dependent fashion. Increased AQP3 mRNA levels are accompanied by an increase in AQP3 protein in undifferentiated keratinocytes and a significant increase in glycerol uptake. Activation of LXR, RAR and RXR also increases AQP3 mRNA levels in undifferentiated and differentiated CHKs, but to a lesser extent. PPARdelta activation stimulates AQP3 expression in undifferentiated CHKs but decreases expression in differentiated CHKs. In contrast, PPARalpha activators do not alter AQP3 expression. AQP9 and AQP10, other members of aquaglyceroporin family, are less abundantly expressed in CHKs, and their expression levels are not significantly altered by treatment with LXR, PPAR, RAR or RXR activators. Finally, when topically applied, the PPARgamma activator, ciglitazone, induces AQP3 but not AQP9 gene expression in mouse epidermis. Our data demonstrate that PPAR and LXR activators stimulate AQP3 expression, providing an additional mechanism by which PPAR and LXR activators regulate epidermal function.
authors: Metabolism Section, Veterans Affairs Medical Center, Northern California Institute for Research and Education, University of California at San Francisco, San Francisco, CA, USA.
authors: Yan J
authors: YJ
authors: Jiang
authors: Peggy
authors: P
authors: Kim
authors: Yang F
authors: YF
authors: Lu
authors: Kenneth R
authors: KR
authors: Feingold
mesh_terms: D000818:Animals; D051400:Aquaporin 3 / Q000235:genetics / Q000378:metabolism*; D020346:Aquaporins / Q000235:genetics; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D000071518:Liver X Receptors; D051379:Mice; D008815:Mice, Inbred Strains; D057093:Orphan Nuclear Receptors / Q000819:agonists; D047493:PPAR alpha / Q000819:agonists; D047494:PPAR delta / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists; D047488:Retinoid X Receptors / Q000819:agonists; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C438667:AQP10 protein, human; C496027:AQP3 protein, human; C109669:AQP9 protein, human; C496028:Aqp3 protein, mouse; D020346:Aquaporins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D045162:Thiazolidinediones; D051400:Aquaporin 3; D005990:Glycerol; D002118:Calcium; C039671:ciglitazone