Department of Dermatology and Allergology, Medical Faculty RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Interdisciplinary Center for Laser Medicine, Medical Faculty RWTH Aachen University, Aachen, Germany.
Lasers Med Sci. 2022 Mar;37(2):887-894. doi: 10.1007/s10103-021-03328-8. Epub 2021 May 14.
Ablative fractional laser treatment leads to a loss of matrix metalloproteinase-3 (MMP-3) expression; therefore, in the present in vitro study, we addressed the role of MMP-3 and its regulation by calcium pantothenate in wound healing processes at the molecular level. Utilizing confocal laser microscopy, we investigated MMP-3 protein expression in fractional ablative CO laser-irradiated skin models. In addition, we established full-thickness 3D skin models using fibroblasts and keratinocytes with a MMP-3 knockdown that were irradiated with a fractional ablative Er:YAG laser to set superficial injuries with standardized dimensions and minimal thermal damage to the surrounding tissue. We revealed an upregulation of MMP-3 protein expression in laser-irradiated skin models receiving aftercare treatment with calcium pantothenate. Skin models with MMP-3 knockdown exhibited a slower wound closure after laser treatment compared to controls. Gene expression profiling detected an MMP-3 knockdown-dependent upregulation of cytokines and chemokines (e.g. IL-36B, CXCL17, IL-37, CXCL5), antimicrobial peptides (e.g., S100A7, S100A12), epidermal crosslinking enzymes (TGM5), and differentiation markers (e.g., LOR, KRT1, FLG2). We also detected a downregulation of cathepsin V and MMP-10, both of which play a prominent role in wound healing processes. After fractional ablative laser injury, an aftercare treatment with calcium pantothenate accelerated wound closure in MMP-3 expressing models faster than in MMP-3 knockdown models. Our data substantiate a major role of MMP-3 in wound healing processes after ablative laser treatments. For the first time, we could show that calcium pantothenate exerts its wound healing-promoting effects at least partly via MMP-3.
消融性分数激光治疗导致基质金属蛋白酶-3（MMP-3）表达丧失；因此，在本体外研究中，我们从分子水平上研究了 MMP-3 及其受泛酸钙调节在伤口愈合过程中的作用。我们利用共聚焦激光显微镜研究了分数消融 CO 激光照射皮肤模型中 MMP-3 蛋白的表达。此外，我们使用成纤维细胞和角质形成细胞建立了全厚 3D 皮肤模型，并用分数消融 Er：YAG 激光照射 MMP-3 敲低的细胞，以在不造成周围组织热损伤的情况下，用标准化的尺寸造成浅表损伤。我们发现，在接受泛酸钙后处理的激光照射皮肤模型中，MMP-3 蛋白表达上调。与对照组相比，MMP-3 敲低的皮肤模型在激光处理后伤口闭合速度较慢。基因表达谱分析检测到 MMP-3 敲低依赖性细胞因子和趋化因子（例如 IL-36B、CXCL17、IL-37、CXCL5）、抗菌肽（例如 S100A7、S100A12）、表皮交联酶（TGM5）和分化标志物（例如 LOR、KRT1、FLG2）的上调。我们还检测到组织蛋白酶 V 和 MMP-10 的下调，它们在伤口愈合过程中都起着重要作用。在分数消融激光损伤后，MMP-3 表达模型的泛酸钙后处理比 MMP-3 敲低模型更快地加速伤口闭合。我们的数据证实了 MMP-3 在消融性激光治疗后伤口愈合过程中的主要作用。我们首次表明，泛酸钙通过 MMP-3 至少部分发挥其促进伤口愈合的作用。
