Liang Xiao, Chai Bangda, Duan Ran, Zhou Yiwen, Huang Xiaolu, Li Qingfeng
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
J Invest Dermatol. 2017 Nov;137(11):2326-2335. doi: 10.1016/j.jid.2017.06.029. Epub 2017 Jul 31.
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 α-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 transcriptase-PCR 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 α-smooth muscle actin and extracellular matrix components, and attenuate transforming growth factor-β1 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.
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变以及细胞外基质的过度产生有关。FKBP10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的成熟。然而，据我们所知，迄今为止尚无研究探讨FKBP10在瘢痕形成中的生物学功能。在本研究中，我们旨在评估FKBP10在增生性瘢痕中的表达和功能。通过微阵列分析、实时逆转录PCR和免疫组织化学，我们发现FKBP10在人和小鼠增生性瘢痕中上调。然后我们评估了用FKBP10小干扰RNA处理的小鼠模型中的增生性瘢痕形成，发现敲低FKBP10可在体内减弱增生性瘢痕形成。为了进一步探索潜在机制，我们在人增生性瘢痕成纤维细胞中敲低了FKBP10。体外结果表明，FKBP10 siRNA可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，并减弱转化生长因子-β1的表达和Smad信号通路的激活。总之，FKBP10在增生性瘢痕形成中起关键作用，可能是增生性瘢痕的治疗靶点。
