Li Guochun, Gustafson-Brown Cindy, Hanks Steven K, Nason Katie, Arbeit Jeffrey M, Pogliano Kit, Wisdom Ronald M, Johnson Randall S
Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Dev Cell. 2003 Jun;4(6):865-77. doi: 10.1016/s1534-5807(03)00159-x.
The migration of epithelial layers requires specific and coordinated organization of the cells at the leading edge of the sheet. Mice that are conditionally deleted for the c-jun protooncogene in epidermis are born at expected frequencies, but with open eyes and with defects in epidermal wound healing. Keratinocytes lacking c-Jun are unable to migrate or elongate properly in culture at the border of scratch assays. Histological analyses in vitro and in vivo demonstrate an inability to activate EGF receptor at the leading edge of wounds, and we demonstrate that this can be rescued by supplementation with conditioned medium or the EGF receptor ligand HB-EGF. Lack of c-Jun prevents EGF-induced expression of HB-EGF, indicating that c-jun controls formation of the epidermal leading edge through its control of an EGF receptor autocrine loop.
上皮层的迁移需要上皮片前缘细胞进行特定且协调的组织。在表皮中条件性缺失c-jun原癌基因的小鼠出生频率正常，但眼睛睁开且存在表皮伤口愈合缺陷。在划痕试验边界处，缺乏c-Jun的角质形成细胞在培养中无法正常迁移或伸长。体内外组织学分析表明，伤口前缘无法激活表皮生长因子（EGF）受体，并且我们证明补充条件培养基或EGF受体配体肝素结合表皮生长因子（HB-EGF）可以挽救这种情况。缺乏c-Jun会阻止EGF诱导的HB-EGF表达，这表明c-jun通过控制EGF受体自分泌环来控制表皮前缘的形成。
