Williams M L, Mommaas-Kienhuis A M, Rutherford S L, Grayson S, Vermeer B J, Elias P M
Dermatology Service, Veterans Administration Medical Center, San Francisco, California.
J Cell Physiol. 1987 Sep;132(3):428-40. doi: 10.1002/jcp.1041320305.
In contrast to most tissues, epidermis and its derivatives appear to lack low density lipoprotein (LDL) receptors and exhibit sterologenesis rates unaffected by circulating lipoprotein (LP) cholesterol content. Since LDL receptors have been demonstrated in both cultured squamous cell carcinoma cells and human foreskin keratinocytes, when maintained in low-calcium media, LDL receptor expression may be related to keratinocyte differentiation. We compared receptor binding and internalization of LDL-gold in normal keratinocytes at different stages of growth at physiological calcium concentrations (early, 3-5 days; preconfluent, 6-10 days; postconfluent, 12-17 days), and correlated receptor expression with sterologenesis in LP-replete vs.-depleted media. Whereas in early cultures about 60% of sterologenesis was LP dependent, this fraction declined in preconfluent and confluent cultures despite continued culture growth and little decline in total sterologenesis. Accordingly, LDL receptors were most evident in early cultures, declining in preconfluent cultures in parallel with the decrease in LP-dependent sterol synthesis. In contrast, sterologenesis in human foreskin fibroblasts was profoundly influenced by exogenous LP at all stages of confluence; total and LP-dependent sterologenesis declined in parallel with growth cessation. These studies represent the first demonstration that normal keratinocytes express functional LDL receptors at physiologic calcium concentrations. Moreover, they demonstrate that LDL receptor expression in keratinocytes, in contrast to fibroblasts, can only in part be attributed to growth requirements. Instead, loss of LDL receptor expression serves as a distinctive marker of keratinocyte differentiation and may reflect the specific functional requirements of the epidermis in vivo.
与大多数组织不同，表皮及其衍生物似乎缺乏低密度脂蛋白（LDL）受体，且其固醇生成速率不受循环脂蛋白（LP）胆固醇含量的影响。由于在培养的鳞状细胞癌细胞和人包皮角质形成细胞中均已证实存在LDL受体，当维持在低钙培养基中时，LDL受体表达可能与角质形成细胞分化有关。我们比较了生理钙浓度下不同生长阶段（早期，3 - 5天；汇合前，6 - 10天；汇合后，12 - 17天）正常角质形成细胞中LDL-金的受体结合和内化情况，并将受体表达与富含LP和缺乏LP的培养基中的固醇生成相关联。在早期培养物中，约60%的固醇生成依赖于LP，尽管培养持续生长且总固醇生成几乎没有下降，但在汇合前和汇合后的培养物中这一比例下降。因此，LDL受体在早期培养物中最为明显，在汇合前培养物中随着LP依赖的固醇合成减少而下降。相比之下，人包皮成纤维细胞的固醇生成在汇合的各个阶段都受到外源性LP的深刻影响；总固醇生成和LP依赖的固醇生成随着生长停止而平行下降。这些研究首次证明正常角质形成细胞在生理钙浓度下表达功能性LDL受体。此外，它们还证明，与成纤维细胞相比，角质形成细胞中LDL受体表达只能部分归因于生长需求。相反，LDL受体表达的丧失是角质形成细胞分化的一个独特标志，可能反映了体内表皮的特定功能需求。
