Department of Dermatology, University of California, Davis, Davis, California, United States of America.
Dermatology Section, VA Northern California Health Care System, Mather, California, United States of America.
PLoS One. 2021 Jul 2;16(7):e0253139. doi: 10.1371/journal.pone.0253139. eCollection 2021.
Keratinocyte migration into skin wounds is the step of the healing process that correlates with the wound closure rate. Keratinocyte migration, and wound epithelialization are decreased when beta 2-adrenergic receptors (B2AR) are activated by 1 μM epinephrine/adrenaline, resulting in delayed wound healing in human and mouse skin. In the present study, we found paradoxically, that in a subset of keratinocyte strains exposure to low concentrations of epinephrine (0.1 nM) increased, rather than decreased, their migratory rate. We find that both the alpha- and the beta-adrenergic receptors are expressed in human keratinocytes, and expression of alpha-2 AR subtypes demonstrated for the first time. Therefore, we tested if the alpha-AR could be modulating the increased migratory response observed in these cell strains. By using specific inhibitors to alpha-AR, we demonstrated that blocking A2B-AR could reverse the rapid cell migration induced by the 0.1 nM epinephrine. Phosphorylation of ERK was elevated after 1-10 minutes of the low epinephrine treatment and the A2B-AR inhibitor blocked the ERK phosphorylation. The results suggest that both the A2B-AR and B2AR mediate keratinocyte migration, in which with a low level of epinephrine treatment, A2B-AR could alter the B2AR signals and regulate the migration rate.
角质细胞向皮肤伤口迁移是愈合过程中的一个步骤,与伤口愈合速度相关。当β2-肾上腺素能受体(B2AR)被 1 μM 肾上腺素/去甲肾上腺素激活时,角质细胞迁移和伤口上皮化会减少,导致人类和小鼠皮肤的伤口愈合延迟。在本研究中,我们发现一个矛盾的现象,即在一部分角质细胞株中,暴露于低浓度的肾上腺素(0.1 nM)会增加而不是减少它们的迁移率。我们发现,α-和β-肾上腺素受体都在人类角质细胞中表达,并首次证明了 α2-AR 亚型的表达。因此,我们测试了 α-AR 是否可以调节这些细胞株中观察到的增加的迁移反应。通过使用特定的 α-AR 抑制剂,我们证明了阻断 A2B-AR 可以逆转 0.1 nM 肾上腺素引起的快速细胞迁移。在低浓度肾上腺素处理后的 1-10 分钟内,ERK 的磷酸化水平升高,A2B-AR 抑制剂阻断了 ERK 的磷酸化。结果表明,A2B-AR 和 B2AR 都介导角质细胞迁移,在低水平的肾上腺素处理下,A2B-AR 可以改变 B2AR 信号并调节迁移率。