Inhibition of FKBP10 Attenuates Hypertrophic Scarring through Suppressing Fibroblast Activity and Extracellular Matrix Deposition
Inhibition of FKBP10 Attenuates Hypertrophic Scarring through Suppressing Fibroblast Activity and Extracellular Matrix Deposition
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DOI：
10.1016/j.jid.2017.06.029
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发表时间：
2017-11-01
影响因子：
6.5
通讯作者：
Li, Qingfeng
中科院分区：
文献类型：
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作者：
Liang, Xiao;Chai, Bangda;Li, Qingfeng
增生性瘢痕是瘢痕形成的一种致病形式，迄今为止尚无公认的治疗方法。其分子机制与成纤维细胞的异常增殖和转化以及细胞外基质的过量产生有关。FKBP 10是一种分子伴侣，能够调节成纤维细胞中α-平滑肌肌动蛋白的表达和前胶原蛋白的成熟。然而，据我们所知，迄今为止还没有研究调查FKBP 10在瘢痕形成中的生物学功能。在这项研究中，我们的目的是评估FKBP 10的表达和功能的增生性瘢痕。通过基因芯片分析、实时荧光定量RT-PCR和免疫组化检测，我们发现FKBP 10在人和小鼠增生性瘢痕中表达上调。然后，我们评估了用FKBP 10小干扰RNA处理的小鼠模型中的增生性瘢痕形成，发现敲低FKBP 10可以减轻体内增生性瘢痕形成。为了进一步探索潜在的机制，在人增生性瘢痕成纤维细胞中敲低FKBP 10。体外实验结果表明，FKBP 10 siRNA能抑制成纤维细胞活性，降低α-平滑肌肌动蛋白和细胞外基质成分的表达，减弱转化生长因子β 1的表达和Smad信号通路的激活。结论FKBP 10在增生性瘢痕形成中起重要作用，可能成为增生性瘢痕的治疗靶点。
Hypertrophic scar is a pathogenic form of scar formation with no recognized treatment to date. Its molecular mechanism is related to the abnormal proliferation and transition of fibroblasts and overproduction of extracellular matrix. FKBP10 is a molecular chaperone able to regulate alpha-smooth muscle actin expression and pro-collagen maturation in fibroblasts. However, to our knowledge, no research has investigated the biological function of FKBP10 in scar formation to date. In this study, we aim to assess the expression and function of FKBP10 in hypertrophic scarring. Through microarray analysis, real-time reverse transcriptaseePCR and immunohistochemistry, we discovered that FKBP10 is up-regulated in human and mouse hypertrophic scars. Then we evaluated hypertrophic scar formation in mouse models treated with FKBP10 small interfering RNA and found that knockdown of FKBP10 could attenuate hypertrophic scar formation in vivo. To further explore the underlying mechanism, FKBP10 was knocked down in human hypertrophic scar fibroblasts. The in vitro results showed that FKBP10 siRNA could inhibit fibroblast activity, reduce the expression of alpha-smooth muscle actin and extracellular matrix components, and attenuate transforming growth factor-beta 1 expression and the activation of the Smad signaling pathway. In conclusion, FKBP10 plays a crucial role in hypertrophic scar formation and might be a therapeutic target for hypertrophic scars.