Crowe D L, Hu L, Gudas L J, Rheinwald J G
Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Boston, MA 02115.
Differentiation. 1991 Dec;48(3):199-208. doi: 10.1111/j.1432-0436.1991.tb00258.x.
Previous studies have revealed that the cells that form the different regions of the oral and epidermal stratified squamous epithelia represent a number of intrinsically distinct keratinocyte subtypes, each of which is developmentally programmed to preferentially express a particular pattern of keratins and type of suprabasal histology. Retinoic acid (RA) is known to modulate stratified squamous epithelial differentiation, including expression of the basal cell keratin K19 and the suprabasal keratins K1/K10 and K4/K13. We have found that all keratinocyte subtypes are similar in their steady state levels of RAR alpha and RAR gamma mRNAs in culture and that these levels are only minimally affected by RA. In contrast, RAR beta mRNA expression varies greatly among keratinocyte subtypes and, in eight of ten cell strains examined, directly correlated with their levels of K19 mRNA. Exposure to 10(-6) M RA increases the levels of RAR beta and K19 mRNA; conversely, complete removal of RA from the medium results in reduced levels of these messages. RA does not coordinately induce RAR beta and K19 messages in nonkeratinocyte cell types: fibroblasts cultured in the presence of 10(-6) M RA express very high levels of RAR beta mRNA but do not express detectable K19, and mesothelial cells decrease their levels of RAR beta and K19 mRNA in response to 10(-6) M RA. The correlation between RAR beta and K19 mRNA levels in most keratinocyte subtypes suggests a role for RAR beta in specifying patterns of keratin expression and suprabasal differentiation in stratified squamous epithelia.
先前的研究表明,构成口腔和表皮复层鳞状上皮不同区域的细胞代表了许多本质上不同的角质形成细胞亚型,每一种亚型在发育过程中都被编程为优先表达特定模式的角蛋白和基底上层组织学类型。已知维甲酸(RA)可调节复层鳞状上皮分化,包括基底细胞角蛋白K19以及基底上层角蛋白K1/K10和K4/K13的表达。我们发现,所有角质形成细胞亚型在培养物中RARα和RARγ mRNA的稳态水平相似,并且这些水平仅受到RA的轻微影响。相比之下,RARβ mRNA表达在角质形成细胞亚型之间差异很大,在所检测的十个细胞株中的八个中,其与K19 mRNA水平直接相关。暴露于10^(-6) M RA会增加RARβ和K19 mRNA的水平;相反,从培养基中完全去除RA会导致这些信息分子水平降低。RA不会在非角质形成细胞类型中协同诱导RARβ和K19信息分子:在10^(-6) M RA存在下培养的成纤维细胞表达非常高水平的RARβ mRNA,但不表达可检测到的K19,并且间皮细胞在响应10^(-6) M RA时会降低其RARβ和K19 mRNA的水平。大多数角质形成细胞亚型中RARβ和K19 mRNA水平之间的相关性表明RARβ在确定复层鳞状上皮中角蛋白表达模式和基底上层分化方面发挥作用。