Xu Miao, Fang Shuo, Xie Aiguo
Department of Plastic and Reconstructive Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Plastic and Reconstructive Surgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China.
Ann Transl Med. 2021 Oct;9(20):1573. doi: 10.21037/atm-21-4978.
The level of cutaneous scar formation is a critical parameter to determine the success of skin wound healing. Adipose-derived mesenchymal stem cells (AMSCs) have been applied to improve treatment of cutaneous injury with the purpose of reducing scar formation.
The levels of procollagen-lysine 1,2-oxoglutarate 5-dioxygenase 1 () were assessed at scar sites. Then, in AMSCs was depleted by either expression of a PLOD1-specific short-hair interfering RNA (shPLOD1) or by expression of microRNA-449 (miR-449) that targets and suppresses protein translation of through 3 prime untranslated region (3'-UTR) interfering. For induction of skin injury, a blade cut of 1.5-cm long and 2-mm thick was made on the middle back of the mice. Transplantation of either AMSCs-shPLOD1 or AMSCs-miR-449 into the injured region of the mice was performed via tail vein injection. The fibrosis as well as underlying mechanisms were assessed.
The AMSCs expressed high levels of , a potent stimulator of fibrosis. We knocked down in AMSCs by expression of either shPLOD1 or miR-449. Transplantation of either AMSCs-shPLOD1 or AMSCs-miR-449 significantly reduced the fibrotic process in the injured region of the mice to a similar degree. Mechanistically, transplantation of either AMSCs-shPLOD1 or AMSCs-miR-449 shifted macrophage polarization from M2 to M1-like and reduced both reactive oxygen species (ROS) and activation of myofibroblasts from fibroblasts.
Suppression of levels in AMSCs either directly by shPLOD1 or indirectly by miR-449 may substantially improve the anti-fibrotic potential of AMSCs during wound healing, likely through altering macrophage polarization.
皮肤瘢痕形成的程度是决定皮肤伤口愈合成功与否的关键参数。脂肪来源的间充质干细胞（AMSCs）已被应用于改善皮肤损伤的治疗，目的是减少瘢痕形成。
在瘢痕部位评估原胶原赖氨酸1,2 - 氧代戊二酸5 - 双加氧酶1（PLOD1）的水平。然后，通过表达PLOD1特异性短发夹干扰RNA（shPLOD1）或通过表达靶向并通过3'非翻译区（3'-UTR）干扰抑制PLOD1蛋白翻译的微小RNA - 449（miR - 449）来耗尽AMSCs中的PLOD1。为了诱导皮肤损伤，在小鼠背部中部制作一个1.5厘米长、2毫米厚的刀片切口。通过尾静脉注射将AMSCs - shPLOD1或AMSCs - miR - 449移植到小鼠的损伤区域。评估纤维化及其潜在机制。
AMSCs表达高水平的PLOD1，这是一种强大的纤维化刺激因子。我们通过表达shPLOD1或miR - 449在AMSCs中敲低PLOD1。AMSCs - shPLOD1或AMSCs - miR - 449的移植均显著降低了小鼠损伤区域的纤维化进程，程度相似。机制上，AMSCs - shPLOD1或AMSCs - miR - 449的移植将巨噬细胞极化从M2转变为M1样，并减少了活性氧（ROS）以及成纤维细胞向肌成纤维细胞的活化。
直接通过shPLOD1或间接通过miR - 449抑制AMSCs中的PLOD1水平可能在伤口愈合过程中显著提高AMSCs的抗纤维化潜力，可能是通过改变巨噬细胞极化实现的。
