Stoll Stefan W, Kansra Sanjay, Elder James T
Department of Dermatology, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0932, USA.
Wound Repair Regen. 2003 Sep-Oct;11(5):346-53. doi: 10.1046/j.1524-475x.2003.11506.x.
Organ culture of skin is known to recapitulate several early events in the process of wound healing. Here we investigate the function of p38 kinase signaling as a regulator of keratinocyte behavior in human skin organ culture. We first show that skin organ culture recapitulates the transition from migration to proliferation that is known to characterize the reepithelialization process. We next show that inhibition of p38 markedly impairs the formation of keratinocyte outgrowth in human skin explant cultures, as well as the migration of keratinocytes in an in vitro wound assay. In contrast, the marked induction of mRNA encoding the ErbB ligand heparin-binding epidermal growth factor-like growth factor, known to occur after skin wounding, was not blocked by inhibition of p38. As assessed by immunoblotting, phosphorylation of p38 was limited and was not increased between 0 and 7 days of organ culture. Our results show the sensitivity of reepithelialization to inhibition by p38 and suggest that p38 acts primarily during the migration phase of this process. These data also indicate that autocrine heparin-binding epidermal growth factor expression is not regulated by p38.
已知皮肤器官培养可重现伤口愈合过程中的几个早期事件。在此，我们研究p38激酶信号传导作为人类皮肤器官培养中角质形成细胞行为调节因子的功能。我们首先表明，皮肤器官培养重现了从迁移到增殖的转变，这一转变是再上皮化过程的特征。接下来我们表明，抑制p38会显著损害人类皮肤外植体培养中角质形成细胞的生长，以及体外伤口试验中角质形成细胞的迁移。相反，已知在皮肤受伤后发生的编码ErbB配体肝素结合表皮生长因子样生长因子的mRNA的显著诱导，并未被p38抑制所阻断。通过免疫印迹评估，p38的磷酸化有限，在器官培养的0至7天之间并未增加。我们的结果显示了再上皮化对p38抑制的敏感性，并表明p38主要在该过程的迁移阶段起作用。这些数据还表明，自分泌肝素结合表皮生长因子的表达不受p38调节。
