CALCIUM AND POTASSIUM ARE IMPORTANT REGULATORS OF BARRIER HOMEOSTASIS IN MURINE EPIDERMIS
CALCIUM AND POTASSIUM ARE IMPORTANT REGULATORS OF BARRIER HOMEOSTASIS IN MURINE EPIDERMIS
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DOI：
10.1172/jci115617
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发表时间：
1992-02-01
影响因子：
15.9
通讯作者：
FEINGOLD, KR
中科院分区：
文献类型：
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作者：
LEE, SH;ELIAS, PM;FEINGOLD, KR
局部溶剂治疗去除角质层中的脂类，导致经皮水分损失(TEWL)显着增加。这种干扰刺激了表皮的各种新陈代谢变化，导致屏障缺陷的快速修复。利用浸泡系统，我们探索了导致完好小鼠屏障修复的信号的本质。使用低渗到高渗溶液的初步实验表明，水传递本身并不是关键信号。然而，添加浓度低至0.01 mM的钙会抑制屏障修复。此外，阻断钙向细胞内转运的维拉帕米和硝苯地平都能阻止钙对TEWL恢复的抑制。此外，抑制钙调蛋白的三氟哌嗪或N-6-aminohexyl-5-chloro-1-naphthalenesulfonamide，可阻止钙诱导的TEWL恢复的抑制。尽管这些结果表明钙在屏障内稳态中起着重要的作用，但单靠钙只能适度抑制TEWL的恢复。单独的钾(10 MM)和单独的磷酸盐(5 MM)对屏障修复也有轻微的抑制作用。然而，钙和钾共同产生了对屏障修复的协同抑制(对照在2.5h内钙+钾的恢复为50%，而钙+钾的恢复为0-11%)。此外，除了抑制TEWL的恢复外，钙和钾还可以防止屏障破坏后3-羟基-3-戊二酰辅酶A还原酶活性的典型增加。最后，脂肪回流到角质层也被钙和钾阻止。这些结果表明，钙、钾和磷酸盐可以防止溶剂破坏后表皮通透性屏障的修复。修复过程可能是由于增加的水通量导致这些离子在上表皮中的浓度降低，从而导致这些离子的被动丢失。
Topical solvent treatment removes lipids from the stratum corneum leading to a marked increase in transepidermal water loss (TEWL). This disturbance stimulates a variety of metabolic changes in the epidermis leading to rapid repair of the barrier defect. Using an immersion system we explored the nature of the signal leading to barrier repair in intact mice. Initial experiments using hypotonic to hypertonic solutions showed that water transit per se was not the crucial signal. However, addition of calcium at concentrations as low as 0.01 mM inhibited barrier repair. Moreover, both verapamil and nifedipine, which block calcium transport into cells, prevented the calcium-induced inhibition of TEWL recovery. Additionally, trifluroperazine or N-6-aminohexyl-5-chloro-1-naphthalenesulfonamide, which inhibit calmodulin, prevented the calcium-induced inhibition of TEWL recovery. Although these results suggest an important role for calcium in barrier homeostasis, calcium alone was only modestly effective in inhibiting TEWL recovery. Potassium alone (10 mM) and phosphate alone (5 mM) also produced a modest inhibition of barrier repair. Together, however, calcium and potassium produced a synergistic inhibition of barrier repair (control 50% recovery vs. calcium + potassium 0-11% recovery in 2.5 h). Furthermore, in addition to inhibiting TEWL recovery, calcium and potassium also prevented the characteristic increase in 3-hydroxy-3-glutaryl CoA reductase activity that occurs after barrier disruption. Finally, the return of lipids to the stratum corneum was also blocked by calcium and potassium. These results demonstrate that the repair of the epidermal permeability barrier after solvent disruption can be prevented by calcium, potassium, and phosphate. The repair process may be signalled by a decrease in the concentrations of these ions in the upper epidermis resulting from increased water flux leading to passive loss of these ions.