The expression of differentiation markers in aquaporin-3 deficient epidermis
- 298 Downloads
Aquaporin-3 (AQP3) is a water/glycerol transporting protein expressed strongly at the plasma membrane of keratinocytes. There is evidence for involvement of AQP3-facilitated water and glycerol transport in keratinocyte migration and proliferation, respectively. Here, we investigated the involvement of AQP3 in keratinocyte differentiation. Studies were done using AQP3 knockout mice, primary cultures of mouse keratinocytes (AQP3 knockout), neonatal human keratinocytes (AQP3 knockdown), and human skin. Cells were cultured with high Ca2+ or 1α,25-dihydroxyvitamin D3 (VD3) to induce differentiation. The expression of differentiation marker proteins and differentiating responses were comparable in control and AQP3-knockout or knockdown keratinocytes. Topical application of all-trans retinoic acid (RA), a known regulator of keratinocyte differentiation and proliferation, induced comparable expression of differentiation marker proteins in wildtype and AQP3 null epidermis, though with impaired RA-induced proliferation in AQP3 null mice. Immunostaining of human and mouse epidermis showed greater AQP3 expression in cells undergoing proliferation than differentiation. Our results showed little influence of AQP3 on keratinocyte differentiation, and provide further support for the proposed involvement of AQP3-facilitated cell proliferation.
KeywordsWater channel Glycerol transport Differentiation Proliferation
All-trans retinoic acid
We thank Maiko Yusa for mouse breeding. This work was supported in part by grant R37 DK35124 from the National Institutes of Health to ASV.
- 4.Cao C, Wan S, Jiang Q, Amaral A, Lu S, Hu G, Bi Z, Kouttab N, Chu W, Wan Y (2008) All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes. J Cell Physiol 215:506–516. doi: 10.1002/jcp.21336 PubMedCrossRefGoogle Scholar
- 7.Griffiths CE, Rosenthal DS, Reddy AP, Elder JT, Astrom A, Leach K, Wang TS, Finkel LJ, Yuspa SH, Voorhees JJ et al (1992) Short-term retinoic acid treatment increases in vivo, but decreases in vitro, epidermal transglutaminase-K enzyme activity and immunoreactivity. J Invest Dermatol 99:283–288. doi: 10.1111/1523-1747.ep12616626 PubMedCrossRefGoogle Scholar
- 10.Hara-Chikuma M, Sohara E, Rai T, Ikawa M, Okabe M, Sasaki S, Uchida S, Verkman AS (2005) Progressive adipocyte hypertrophy in aquaporin-7-deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation. J Biol Chem 280:15493–15496. doi: 10.1074/jbc.C500028200 PubMedCrossRefGoogle Scholar
- 18.Rittié L, Varani J, Kang S, Voorhees JJ, Fisher GJ (2006) Retinoid-induced epidermal hyperplasia is mediated by epidermal growth factor receptor activation via specific induction of its ligands heparin-binding EGF and amphiregulin in human skin in vivo. J Invest Dermatol 126:732–739. doi: 10.1038/sj.jid.5700202 PubMedCrossRefGoogle Scholar
- 20.Rosenthal DS, Griffiths CE, Yuspa SH, Roop DR, Voorhees JJ (1992) Acute or chronic topical retinoic acid treatment of human skin in vivo alters the expression of epidermal transglutaminase, loricrin, involucrin, filaggrin, and keratins 6 and 13 but not keratins 1, 10, and 14. J Invest Dermatol 98:343–350. doi: 10.1111/1523-1747.ep12499802 PubMedCrossRefGoogle Scholar
- 22.Takahashi H, Ibe M, Kinouchi M, Ishida-Yamamoto A, Hashimoto Y, Iizuka H (2003) Similarly potent action of 1, 25-dihydroxyvitamin D3 and its analogues, tacalcitol, calcipotriol, and maxacalcitol on normal human keratinocyte proliferation and differentiation. J Dermatol Sci 31:21–28. doi: 10.1016/S0923-1811(02)00136-6 PubMedCrossRefGoogle Scholar
- 25.Xiao JH, Feng X, Di W, Peng ZH, Li LA, Chambon P, Voorhees JJ (1999) Identification of heparin-binding EGF-like growth factor as a target in intercellular regulation of epidermal basal cell growth by suprabasal retinoic acid receptors. EMBO J 18:1539–1548. doi: 10.1093/emboj/18.6.1539 PubMedCrossRefGoogle Scholar