Liu Jinyan, Luo Chengqun, Yin Zhaoqi, Li Ping, Wang Shaohua, Chen Jia, He Quanyong, Zhou Jianda
Department of Plastic Surgery, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
Mol Med Rep. 2016 Mar;13(3):2683-8. doi: 10.3892/mmr.2016.4877. Epub 2016 Feb 5.
MicroRNAs (miRs), a class of non‑coding RNAs 18‑25 nucleotides in length, generally serve suppressive role in the regulation of gene expression via directly binding to the 3'‑untranslated region (UTR) of their target mRNA. Previous studies have identified several miRs to be involved in thermal injury repair. However, the role of miR let‑7b during the recovery of thermal injury, in addition to the underlying mechanisms, has not previously been studied. In the present study, the expression of let‑7b was observed to be significantly increased in skin tissue shortly following thermal injury, however, gradually reduced during the recovery of thermal injury. Notably, similar findings were observed in heat‑denatured skin fibroblasts. Furthermore, collagen, type I, alpha 1 (COL1A1) and collagen, type I, alpha 2 (COL1A2), which are associated with the synthesis of type I collagen, were identified as two targets of let‑7b in skin fibroblasts. The overexpression of let‑7b was observed to upregulate the protein expression levels of COL1A1 and COL1A2, while knockdown of let‑7b reduced the levels of COL1A1 and COL1A2 in skin fibroblasts. Furthermore, COL1A1 and COL1A2 were significantly downregulated shortly following thermal injury, while gradually upregulated during healing, in heat‑damaged skin tissue and skin fibroblasts, with the expression profiles opposite to that of let‑7b. Taken together, this suggests that the downregulation of let‑7b in heat‑damaged dermis promotes the synthesis of type I collagen and thus aids in burn wound repair.
微小RNA(miR)是一类长度为18 - 25个核苷酸的非编码RNA,通常通过直接结合其靶mRNA的3'非翻译区(UTR)在基因表达调控中发挥抑制作用。先前的研究已鉴定出几种miR参与热损伤修复。然而,miR let - 7b在热损伤恢复过程中的作用及其潜在机制此前尚未被研究。在本研究中,观察到热损伤后不久皮肤组织中let - 7b的表达显著增加,但在热损伤恢复过程中逐渐降低。值得注意的是,在热变性的皮肤成纤维细胞中也观察到了类似的结果。此外,与I型胶原蛋白合成相关的I型胶原蛋白α1(COL1A1)和I型胶原蛋白α2(COL1A2)被确定为皮肤成纤维细胞中let - 7b的两个靶标。观察到let - 7b的过表达上调了COL1A1和COL1A2的蛋白表达水平,而敲低let - 7b则降低了皮肤成纤维细胞中COL1A1和COL1A2的水平。此外,在热损伤的皮肤组织和皮肤成纤维细胞中,热损伤后不久COL1A1和COL1A2显著下调,而在愈合过程中逐渐上调,其表达谱与let - 7b相反。综上所述,这表明热损伤真皮中let - 7b的下调促进了I型胶原蛋白的合成,从而有助于烧伤创面修复。