Wei Jun, Wang Zhiyong, Zhong Chaoyi, Ding Huarong, Wang Xiqiao, Lu Shuliang
Department of Plastic and Burn Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
Department of Burns, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wound Repair Regen. 2021 Sep;29(5):792-800. doi: 10.1111/wrr.12913. Epub 2021 Apr 5.
Hypertrophic scars (HSs) form due to unchecked proliferation of fibrous tissue after an injury to the skin. Recently, lncRNA MIR503HG was shown to be involved in HS. However, the mechanism by which MIR503HG affects the formation and progression of HS still needs further study. qRT-PCR was applied to examine the levels of MIR503HG and miR-143-3p in HS tissues and human hypertrophic scar fibroblasts (hHSFs). The relationships of MIR503HG, miR-143-3p and Smad3 were explored with a dual-luciferase reporter assay. Cell proliferation, apoptosis, and invasion were measured by CCK-8 assay, flow cytometry and transwell assay, respectively. The protein level of Smad3 was tested via Western blotting. MIR503HG was upregulated and miR-143-3p was downregulated in HS versus normal skin tissues. The knockdown of MIR503HG and the overexpression of miR-143-3p suppressed the proliferation and invasion of hHSF, and promoted cell apoptosis. MIR503HG bound to miR-143-3p while miR-143-3p directly targeted Smad3 to inhibit its expression. Suppression of miR-143-3p and overexpression of Smad3, respectively, reversed these effects of knockdown of MIR503HG and overexpression of miR-143-3p on hHSFs. Our research supports a model in which the MIR503HG/miR-143-3p/Smad3 axis serves as a critical regulator of HS, highlighting a promising therapeutic option for HS.
肥厚性瘢痕（HSs）是由于皮肤受伤后纤维组织不受控制地增殖而形成的。最近，lncRNA MIR503HG被证明与HS有关。然而，MIR503HG影响HS形成和进展的机制仍需进一步研究。应用qRT-PCR检测HS组织和人肥厚性瘢痕成纤维细胞（hHSFs）中MIR503HG和miR-143-3p的水平。通过双荧光素酶报告基因检测探讨MIR503HG、miR-143-3p与Smad3之间的关系。分别通过CCK-8检测、流式细胞术和Transwell检测来测量细胞增殖、凋亡和侵袭。通过蛋白质免疫印迹法检测Smad3的蛋白水平。与正常皮肤组织相比，HS中MIR503HG上调，miR-143-3p下调。敲低MIR503HG和过表达miR-143-3p可抑制hHSF的增殖和侵袭，并促进细胞凋亡。MIR503HG与miR-143-3p结合，而miR-143-3p直接靶向Smad3以抑制其表达。分别抑制miR-143-3p和过表达Smad3可逆转敲低MIR503HG和过表达miR-143-3p对hHSFs的这些影响。我们的研究支持一种模型，即MIR503HG/miR-143-3p/Smad3轴作为HS的关键调节因子，突出了HS一种有前景的治疗选择。
