Yang Po-Yu, Chen Chin-Chu, Tsai You-Shan, Liao Yi-Wen, Ng Min Yee, Huang Chun-Chung, Yu Cheng-Chia, Hong San-Fu
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
J Dent Sci. 2024 Oct;19(4):2100-2105. doi: 10.1016/j.jds.2024.04.009. Epub 2024 Apr 23.
BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF), characterized by excessive collagen deposition by myofibroblasts, is often linked to Areca nuts consumption. Probiotics consumption has shown protective effects against fibrotic diseases, and recently, their metabolic byproducts, known as postbiotics, have demonstrated superior advantages over probiotics. However, studies on the therapeutic impact of postbiotics on OSF have been scarce. Therefore, this study aims to examine the effect of PostBio GK4, a postbiotic derived from , on OSF and explore its underlying mechanisms.
The cytotoxicity of GK4 in normal buccal mucosal fibroblasts (BMFs) and fibrotic BMFs (fBMFs) were assessed. Following this, we evaluated the effects of GK4 on collagen contraction, migratory, and wound healing capacities in arecoline-induced fibrotic BMFs. Next, Western blotting and ELISA were employed to assess GK4's impact on fibrosis-related proteins such as COL1A1, and α-SMA, as well as on TGF-β and Smad2/3 signaling pathway.
Arecoline was shown to stimulate cell migratory, contractile and wound healing abilities as well as the expression of α-SMA and COL1A1 in BMFs. Treatment with GK4 reduced all arecoline-induced phenomena in BMFs. Moreover, GK4 diminished the increased expression of TGF-β and Smad2/3.
Our findings proposed that GK4 may exert a suppressive effect on arecoline-induced myofibroblast activities via the inhibition of TGF-β and Smad2/3 signaling pathway. Therefore, GK4 holds promise as an adjunct therapeutic approach for intervening in OSF. Further in-vivo and clinical studies are warranted to validate these observations.
背景/目的:口腔黏膜下纤维化(OSF)的特征是肌成纤维细胞过度沉积胶原蛋白,通常与食用槟榔有关。食用益生菌已显示出对纤维化疾病的保护作用,最近,其代谢副产物(称为后生元)已显示出优于益生菌的优势。然而,关于后生元对OSF治疗影响的研究很少。因此,本研究旨在研究源自 的后生元PostBio GK4对OSF的影响,并探讨其潜在机制。
评估GK4对正常颊黏膜成纤维细胞(BMF)和纤维化BMF(fBMF)的细胞毒性。在此之后,我们评估了GK4对槟榔碱诱导的纤维化BMF中胶原蛋白收缩、迁移和伤口愈合能力的影响。接下来,采用蛋白质免疫印迹法和酶联免疫吸附测定法评估GK4对纤维化相关蛋白(如COL1A1和α-SMA)以及对TGF-β和Smad2/3信号通路的影响。
槟榔碱被证明可刺激BMF中的细胞迁移、收缩和伤口愈合能力以及α-SMA和COL1A1的表达。用GK4处理可减少BMF中所有槟榔碱诱导的现象。此外,GK4降低了TGF-β和Smad2/3的表达增加。
我们的研究结果表明,GK4可能通过抑制TGF-β和Smad2/3信号通路对槟榔碱诱导的肌成纤维细胞活性发挥抑制作用。因此,GK4有望作为干预OSF的辅助治疗方法。有必要进行进一步的体内和临床研究来验证这些观察结果。