Acute downregulation of miR-155 at wound sites leads to a reduced fibrosis through attenuating inflammatory response.
Acute downregulation of miR-155 at wound sites leads to a reduced fibrosis through attenuating inflammatory response.
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DOI：
10.1016/j.bbrc.2014.09.077
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发表时间：
2014-10
影响因子：
3.1
通讯作者：
Longlong Yang;Jia-qi Liu;X. Bai;L. Fan;F. Han;W. Jia;L. Su;Jihong Shi;Chao-wu Tang;D. Hu-D.
中科院分区：
文献类型：
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作者：
Longlong Yang;Jia-qi Liu;X. Bai;L. Fan;F. Han;W. Jia;L. Su;Jihong Shi;Chao-wu Tang;D. Hu-D.
纤维化与伤口愈合密切相关，是一个重要的症状性临床问题。据报道，炎症反应是原因之一。MiR-155与炎症细胞的发育和需求相关，因此我们认为减少miR-155在伤口部位的表达可以通过减少炎症反应来提高愈合质量。为了验证这一假说，通过直接向伤口边缘注射Anagomir来局部拮抗miR-155来减少miR-155的表达。发现MIR155antagomir处理的创面免疫细胞需求明显不足，促炎因子IL-1β、肿瘤坏死因子-α降低，抗炎因子IL-10升高。用miR-155antagomir治疗后，创面α-SMA、COL1和COL3的表达均从基因水平和蛋白表达水平上降低。α-SMA、COL1和COL3在创面的表达均低于对照组。注射Anagomir的创面胶原结构改善，胶原纤维排列规则。同时，愈合率无明显变化。这些结果为miR-155在纤维化的发病机制中发挥重要作用提供了直接证据，表明miR-155在预防和减轻皮肤纤维化方面具有潜在的治疗作用。
Fibrosis, tightly associated with wound healing, is a significant symptomatic clinical problem. Inflammatory response was reported to be one of the reasons. MiR-155 is relatively related with the development and requirement of inflammatory cells, so we thought reduce the expression of miR-155 in wound sites could improve the quality of healing through reduce inflammatory response. To test this hypothesis, locally antagonizing miR-155 by directly injecting antagomir to wound edge was used to reduce the expression of miR-155. We found wounds treated with miR-155 antagomir had an obvious defect in immune cells requirements, pro-inflammatory factors IL-1β and TNF-α reduced while anti-inflammatory factor IL-10 increased. With treatment of miR-155 antagomir, the expression of α-smooth muscle actin (α-SMA), Col1 and Col3 at wound sites all reduced both from mRNA levels and protein expressions. Wounds injected with antagomir resulted in the structure improvement of collagen, the collagen fibers were more regularly arranged. Meanwhile the rate of healing did not change significantly. These results provide direct evidences that miR-155 play an important role in the pathogenesis of fibrosis and show that miR-155 antagomir has the potential therapy in prevention and reduction of skin fibrosis.