Liu Danling, Qian Tingting, Li Peifan, Li Wen, Sun Shan, Jiang Jack J
ENT Institute and Otorhinolaryngology, Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Fudan University School of Basic Medical Sciences, NHC Key Laboratory of Hearing Medicine, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Biomedical Sciences, Shanghai, China.
Laryngoscope. 2022 Jun;132(6):1237-1244. doi: 10.1002/lary.29884. Epub 2021 Sep 30.
OBJECTIVES/HYPOTHESIS: Vocal fold (VF) fibroblasts are the central target for developing new strategies for the treatment of VF scarring and fibrosis. Asiatic acid (AA) is a triterpenoid derivate with antifibrotic properties. However, the effect of AA in VF scarring is poorly understood. The objective of this study was to investigate the potential application of AA as a therapeutic treatment in VF scarring.
Xxxxx.
The functional expression of SMAD7 was knocked down with recombinant adenoviruses and adeno-associated viruses carrying shRNAs in the in vitro and in vivo models, which were constructed to investigate AA's antifibrotic function. The expression of collagens and SMADs in cultured human and rabbit cell lines and animal models was evaluated with quantitative reverse transcription polymerase chain reaction and immunohistochemistry labeling, respectively. Cell migration capacity and contraction in VF fibroblast cell lines were also evaluated.
AA downregulated the downstream fibrotic activation in a dose-dependent manner. Meanwhile, AA attenuated VF scarring/fibrosis by reducing collagen deposition. Furthermore, the antifibrotic effects of AA were associated with the upregulation of SMAD7. In contrast, knockdown of SMAD7 inhibited the effect of AA on transforming growth factor-beta-1 (TGF-β1) stimulation, which suggests a central role for SMAD7 in AA-induced antifibrotic activities during VF fibrosis.
We concluded that AA, which is a novel therapeutic candidate for preventing VF scarring/fibrosis, might exert its antifibrotic effect via the TGF-β1/SMAD signaling pathway.
NA Laryngoscope, 132:1237-1244, 2022.
目的/假设：声带（VF）成纤维细胞是开发治疗VF瘢痕形成和纤维化新策略的核心靶点。积雪草苷（AA）是一种具有抗纤维化特性的三萜类衍生物。然而，AA在VF瘢痕形成中的作用尚不清楚。本研究的目的是探讨AA作为治疗VF瘢痕形成的潜在应用。
xxxx。
在体外和体内模型中，用携带短发夹RNA的重组腺病毒和腺相关病毒敲低SMAD7的功能表达，构建这些模型以研究AA的抗纤维化功能。分别用定量逆转录聚合酶链反应和免疫组织化学标记评估培养的人和兔细胞系及动物模型中胶原蛋白和SMADs的表达。还评估了VF成纤维细胞系中的细胞迁移能力和收缩情况。
AA以剂量依赖性方式下调下游纤维化激活。同时，AA通过减少胶原蛋白沉积减轻VF瘢痕形成/纤维化。此外，AA的抗纤维化作用与SMAD7的上调有关。相反，敲低SMAD7抑制了AA对转化生长因子-β1（TGF-β1）刺激的作用，这表明SMAD7在VF纤维化过程中AA诱导的抗纤维化活性中起核心作用。
我们得出结论，AA作为预防VF瘢痕形成/纤维化的新型治疗候选物，可能通过TGF-β1/SMAD信号通路发挥其抗纤维化作用。
NA 喉镜，132:1237 - 1244，2022年。
