Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China.
J Mol Histol. 2019 Aug;50(4):315-323. doi: 10.1007/s10735-019-09828-w. Epub 2019 May 8.
Hypertrophic scar is a common complication after skin injury. MicroRNAs have been reported related to hypertrophic scar through posttranscriptional control of genes. Hypertrophic scar-derived fibroblast model and mice incision model were used to see the expression of microRNA-494 and whether the level changes of microRNA-494 could affect scar formation. It was found that in hypertrophic scar, the expression of microRNA-494 decreased. However, after over-express microRNA-494 in fibroblasts, the levels of scar related molecules such as Col I, Col III increased. And when suppress the level of microRNA-494 in fibroblasts, the levels of collagen decreased. Moreover, the up-regulation of microRNA-494 led to decreased apoptosis of fibroblasts while the down-regulation of it led to increased apoptosis. Further, it was found that PTEN was one of the downstream targets of microRNA-494. The up-regulation of PTEN led to inactivation of PI3K/AKT pathway and the decreased expression of collagens. In conclusion, we confirmed that microRNA-494 could be a key regulator to suppress hypertrophic scar formation. The suppression of microRNA-494 could eliminate its inhibition effect to PTEN and finally decrease the expression of collagen and inhibit hypertrophic scar formation.
增生性瘢痕是皮肤损伤后的常见并发症。已有研究报道，microRNAs 通过对基因的转录后调控与增生性瘢痕有关。本研究采用增生性瘢痕成纤维细胞模型和小鼠切口模型，观察 microRNA-494 的表达及其水平变化是否影响瘢痕形成。结果发现，在增生性瘢痕中，microRNA-494 的表达降低。然而，在成纤维细胞中过度表达 microRNA-494 后，Col I、Col III 等与瘢痕相关的分子水平增加。而抑制成纤维细胞中 microRNA-494 的水平时，胶原的水平降低。此外，microRNA-494 的上调导致成纤维细胞凋亡减少，而下调则导致凋亡增加。进一步研究发现，PTEN 是 microRNA-494 的下游靶标之一。PTEN 的上调导致 PI3K/AKT 通路失活和胶原表达减少。综上所述，我们证实 microRNA-494 可作为抑制增生性瘢痕形成的关键调节剂。抑制 microRNA-494 可消除其对 PTEN 的抑制作用，最终减少胶原的表达并抑制增生性瘢痕形成。
