The control of adrenocortical cytodifferentiation by extracellular matrix.
The control of adrenocortical cytodifferentiation by extracellular matrix.
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细胞外基质对肾上腺皮质细胞分化的控制。
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发表时间：
1980
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通讯作者：
E. Turley
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作者：
E. Turley
成年大鼠肾上腺皮质细胞维持在培养基中补充马血清（HS）从粘性上皮岛分泌大量的皮质酮。这样的细胞不产生可检测的细胞外物质（ECM）并且不运动。暴露于胎牛血清补充剂（FCS）的培养物产生异染性ECM，调节成纤维细胞形态，并变得能动。在24小时内，这些细胞的类固醇产量下降了100倍。细胞现在类似于肾上腺皮质囊的肌纤维母细胞“干”细胞，并且通过表现出肌纤维母细胞表型同时保留对促肾上腺皮质激素（ACTH）的反应性和有限的皮质类固醇分泌能力来表达结构和功能双态性。暴露于FCS中的肌纤维母细胞的ACTH覆盖FSC的效果：ECM消失，类固醇产生增加几倍，细胞发育成上皮形态。通过使用6-重氮-5-氧代-L-正亮氨酸（DON）和外源性添加ECM组分的抑制研究，研究了响应FCS产生的ECM可能导致从高度分化的非运动性肾上腺皮质细胞向分化程度较低的运动性肾上腺皮质干细胞的改变的可能性。DON是一种谷氨酰胺类似物，可抑制FCS中异染ECM的合成，并阻止对成纤维细胞形态的调节、运动的发生和类固醇产生的减少。此外，透明质酸，而不是硫酸软骨素，上皮样分泌细胞促进类固醇生产下降和轻微的改变形态和运动。这两个结果是一致的可能性，异染ECM生产是负责的类固醇分泌的肌纤维母细胞表型的逆转。通过将细胞保持在磺化至类似于ECM的负电荷密度的聚苯乙烯表面上来模拟这种效果。这一结果意味着ECM的负电荷可能有助于肾上腺皮质干细胞表型的表达，并且其作用是细胞外的。ECM介导的控制肾上腺皮质分化的一个可能的生理作用。
Adult rat adrenal cortical cells maintained in medium supplemented with horse serum (HS) from cohesive epithelial islands secrete large amounts of corticosterone. Such cells do not produce detectable extracellular material (ECM) and are not motile. Cultures exposed to fetal calf serum supplements (FCS) produce metachromatic ECM, modulate to a fibroblastic morphology, and become motile. Within 24 h, steroid production by these cells drop 100-fold. Cells now resemble myofibroblastic "stem" cells of the adrenal cortical capsule, and express structural and functional bimorphism by exhibiting a myofibroblastic phenotype while retaining responsiveness to adrenocorticotropic hormone (ACTH) and limited corticosteroid secreting capacity. Exposure of the myofibroblastic cells to ACTH in FCS overrides the effect of FSC: ECM disappears, steroid production increases several fold, and cells develop an epithelial morphology. The possibility that ECM produced in response to FCS may be responsible for the alteration from a highly differentiated, non-motile adrenocortical cell to a less differentiated, motile adrenocortical stem cell was investigated by inhibition studies using 6-diazo-5-oxo-L-nor-leucine (DON) and by exogenously added components of ECM. DON, a glutamine analogue, inhibited the synthesis of metachromatic ECM in FCS, and prevented the modulation to a fibroblastic morphology, onset of motility, and decrease in steroid production. Addition of hyaluronic acid, but not of chondroitin sulfate, to the epithelioid secretory cells promoted a drop in steroid production and slight alteration in morphology and movement. Both results are consistent with the possibility that metachromatic ECM production is responsible for the reversion of the steroid secretory to the myofibroblastic phenotype. This effect was mimicked by maintaining cells on polystyrene surfaces that were sulfonated to a negative charge density similar to that of ECM. This result implies that the negative charge of ECM may contribute to the expression of the adrenocortical stem cell phenotype, and that its effect is extracellular. A possible physiologic role for ECM-mediated control of adrenal cortical differentiation is proposed.