Re-epithelialization describes the resurfacing of a skin wound with new epithelium. In response to various stimuli including that of growth factors, cytokines and extracellular matrix (ECM), wound edge epidermal keratinocytes undergo cytoskeleton rearrangements compatible with their motile behavior and develop protrusive adhesion contacts. Matrix metalloproteinases (MMP) expression is crucial for proper cell movement and ECM remodeling; however, their deposition mechanism is unknown in keratinocytes. Here, we show that similar to cytokine IL-1ß, the precursor laminin 332 pro-migratory fragment G45 induces expression of the MMP-9 pro-enzyme, which together with MMP-14, further exerts its proteolytic activity within epithelial podosomes. This event strictly depends on the expression of the proteoglycan receptor syndecan-1 that was found in a ring surrounding the podosome core, co-localised with CD44. Our findings uncover that by directly recruiting both syndecan-1 and CD44, the laminin-332 G45 domain plays a major role in regulating mechanisms underlying keratinocyte / ECM remodeling during wound repair.

关于-上皮化描述了具有新上皮的皮肤伤口的表面重修。响应各种刺激，包括生长因子、细胞因子和细胞外基质 (ECM) 的刺激，伤口边缘表皮角质形成细胞经历与其运动行为相容的细胞骨架重排，并形成突出的粘附接触。基质金属蛋白酶 (MMP) 表达对于适当的细胞运动和 ECM 重塑至关重要；然而，它们在角质形成细胞中的沉积机制尚不清楚。在这里，我们表明与细胞因子 IL-1ß 类似，前体层粘连蛋白 332 前体迁移片段 G45 诱导 MMP-9 酶原的表达，与 MMP-14 一起，进一步在上皮足体内发挥其蛋白水解活性。该事件严格取决于蛋白多糖受体 syndecan-1 的表达，该蛋白多糖受体在围绕足小体核心的环中发现，与 CD44 共定位。我们的研究结果表明，通过直接招募 syndecan-1 和 CD44，层粘连蛋白 332 G45 结构域在伤口修复过程中调节角质形成细胞/ECM 重塑的机制中起主要作用。