Blanchet S, Favier B, Chevalier G, Kastner P, Michaille J J, Chambon P, Dhouailly D
Epithelial Differentiation Biology, LEDAC-UMR/CNRS, Albert Bonniot Institute, La Tronche, France.
J Invest Dermatol. 1998 Aug;111(2):206-12. doi: 10.1046/j.1523-1747.1998.00275.x.
Embryonic mouse upper-lip skin explants treated with 16.7 microM all-trans retinoic acid (tRA) give rise to a glandular metaplasia of hair vibrissa follicles; however, at this concentration, tRA can activate not only the three retinoic acid receptors (RARalpha, beta, and gamma), but also the retinoid X receptors (RXRalpha, beta, and gamma) as a consequence of its isomerization to 9-cis retinoic acid. We therefore studied the respective roles of the RXR and RAR by treating RARalpha(-/-), beta(-/-), and gamma(-/-) skin explants with tRA and wild-type explants with synthetic retinoids specific for RXR or for each of the RAR. The null mutation of the RARalpha, RARbeta, and RARgamma genes did not prevent tRA-induced hair glandular metaplasia, but RARgamma inactivation dramatically reduced its ratio. As demonstrated by treating explants with a RAR- or a RXR-specific panagonist (CD367 and Ro25-7386, respectively), RAR are primarily responsible for this metaplasia. The use of two retinoids (Ro40-6055, 8 x 10(-3) microM, or CD437, 7.7 x 10(-2) microM) that are believed to act, respectively, as a RARalpha- or a RARgamma-specific agonist showed that both these receptors can initiate a metaplasia. In contrast, BMS453, a RARbeta-specific agonist, was unable to give rise to any metaplasia. Nevertheless, the highest degrees and ratios of metaplasia were only obtained after treatment with the CD367 RAR panagonist, or with either Ro40-6055 or CD437 at a concentration sufficient to allow the activation of the three RAR, suggesting that RARbeta activation is required for a metaplasia of all vibrissae.
用16.7微摩尔全反式维甲酸（tRA）处理的胚胎小鼠上唇皮肤外植体可导致触须毛囊的腺化生；然而，在此浓度下，tRA不仅能激活三种维甲酸受体（RARα、β和γ），还能因其异构化为9-顺式维甲酸而激活类视黄醇X受体（RXRα、β和γ）。因此，我们通过用tRA处理RARα（-/-）、β（-/-）和γ（-/-）皮肤外植体以及用对RXR或每种RAR具有特异性的合成类视黄醇处理野生型外植体，研究了RXR和RAR各自的作用。RARα、RARβ和RARγ基因的无效突变并未阻止tRA诱导的触须腺化生，但RARγ失活显著降低了其比例。用RAR或RXR特异性激动剂（分别为CD367和Ro25-7386）处理外植体表明，RAR对此化生起主要作用。使用两种分别被认为作为RARα或RARγ特异性激动剂的类视黄醇（Ro40-6055，8×x10（-3）微摩尔，或CD437，7.7×10（-2）微摩尔）表明，这两种受体均可引发化生。相比之下，RARβ特异性激动剂BMS453无法引起任何化生。然而，只有在用CD367 RAR激动剂或用足以激活三种RAR的浓度的Ro40-6055或CD437处理后，才能获得最高程度和比例的化生，这表明所有触须的化生都需要RARβ激活。
