Mitra R S, Wrone-Smith T, Simonian P, Foreman K E, Nunez G, Nickoloff B J
Department of Pathology, University of Michigan, Ann Arbor, USA.
Lab Invest. 1997 Jan;76(1):99-107.
During embryological development and throughout life, regulation of the thickness of skin is likely to involve modulation of keratinocyte proliferation, differentiation, and cell death. One major mechanism of cell death is apoptosis; but the precise relationship between apoptosis and differentiation has not been well-defined. In this report, we demonstrate that when cultured undifferentiated keratinocytes have their adhesive interactions interrupted by either enzymatic treatment (ie, trypsin) and suspension in a semi-solid methyl cellulose medium, or exposure to antibodies against beta 1 integrins and E-cadherin, induction of differentiation occurs (expression of involucrin), as well as apoptosis (positive terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP-biotin nick end labeling (TUNEL) assay and DNA fragmentation). However, these events are not directly interdependent processes, as determined by two-color immunofluorescence staining. Thus, apoptosis can occur without evidence of differentiation and vice versa. The process o apoptosis in keratinocytes was dissected at the molecular level and found to be correlated with increased expression of Bax and decreased levels of Bcl-XL, with no role for either Bcl-2 or Bcl-XS. We conclude that keratinocytes do not need to undergo differentiation before undergoing apoptosis.
在胚胎发育过程及整个生命过程中，皮肤厚度的调节可能涉及角质形成细胞增殖、分化及细胞死亡的调控。细胞死亡的一个主要机制是凋亡；但凋亡与分化之间的确切关系尚未明确界定。在本报告中，我们证明，当培养的未分化角质形成细胞通过酶处理（即胰蛋白酶）并悬浮于半固体甲基纤维素培养基中，或暴露于抗β1整合素和E-钙黏蛋白的抗体而使其黏附相互作用中断时，会发生分化诱导（兜甲蛋白表达）以及凋亡（阳性末端脱氧核苷酸转移酶（Tdt）介导的dUTP-生物素缺口末端标记（TUNEL）检测及DNA片段化）。然而，如通过双色免疫荧光染色所确定的，这些事件并非直接相互依存的过程。因此，凋亡可在无分化证据的情况下发生，反之亦然。角质形成细胞中的凋亡过程在分子水平上得以剖析，发现其与Bax表达增加及Bcl-XL水平降低相关，而Bcl-2或Bcl-XS均无作用。我们得出结论，角质形成细胞在经历凋亡之前无需经历分化。
