Sheng Wei, Feng Zihao, Song Qi, Niu Heyong, Miao Guoying
Wound Care Center, College of Life Sciences, Chinese PLA General Hospital Beijing 100853, China.
Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
Am J Transl Res. 2016 May 15;8(5):2079-87. eCollection 2016.
Understanding of the mechanism of cutaneous scar formation with the goal of developing potential therapies to promote scar-less wound healing appears to be extremely critical. Mesenchymal stem cells (MSCs) have a demonstrate role in promoting scar-less wound healing. However, recent studies have shown that the function of MSCs may be attenuated due to insufficient activation in vivo. Here, we aimed to increase the activity and functions of MSCs to improve their effects during scar formation. We found that overexpression of microRNA-375 (miR-375) in MSCs significantly decreased the levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) protein, but not mRNA. Mechanistically, miR-375 inhibited TIMP-1 protein translation through binding to the 3'-UTR of the TIMP-1 mRNA in MSCs. Transplantation of miR-375-expressing MSCs significantly reduced the fibrosis in the scar region of the mice, possibly through reduction of reactive oxygen species (ROS), suppression of transition of myofibroblasts from fibroblasts, and increases in hepatic growth factor (HGF). Together, these data suggest that overexpression of miR-375 in MSCs may substantially improve the effects of MSCs on reduction of scar during wound healing. Our study sheds new light on a scar-less wound healing.
为了开发促进无瘢痕伤口愈合的潜在疗法，了解皮肤瘢痕形成机制显得极为关键。间充质干细胞（MSCs）在促进无瘢痕伤口愈合中具有明确作用。然而，最近的研究表明，由于体内激活不足，MSCs的功能可能会减弱。在此，我们旨在提高MSCs的活性和功能，以改善其在瘢痕形成过程中的作用。我们发现，在MSCs中过表达微小RNA-375（miR-375）可显著降低金属蛋白酶组织抑制剂1（TIMP-1）蛋白水平，但不影响mRNA水平。机制上，miR-375通过与MSCs中TIMP-1 mRNA的3'-UTR结合来抑制TIMP-1蛋白翻译。移植表达miR-375的MSCs可显著减轻小鼠瘢痕区域的纤维化，这可能是通过减少活性氧（ROS）、抑制成纤维细胞向肌成纤维细胞的转变以及增加肝细胞生长因子（HGF）来实现的。总之，这些数据表明，在MSCs中过表达miR-375可能会显著改善MSCs在伤口愈合过程中减少瘢痕的作用。我们的研究为无瘢痕伤口愈合提供了新的见解。
