- 學位論文
探討小孢子靈芝免疫調節蛋白於口腔黏膜下纖維化症的治療功效及分子機轉
The efficiency and mechanisms of immunomodulatory protein from Ganoderma microsporum (GMI) on oral submucous fibrosis treatment
摘要
口腔黏膜纖維化症為一種口腔癌發生之癌前病變。流行病學指出口腔黏膜纖維 化症主要與檳榔嚼食習慣相關，然而其致病機轉仍未知且無任何有效治療方式。我 們先前研究發現肌纖維母細胞活化可促使口腔黏膜纖維化，因此尋找有效抑制肌纖 維母細胞活化之天然物將有助於口腔黏膜纖維化症的防治。本實驗的研究結果發現 小孢子靈芝免疫調節蛋白能明顯抑制纖維化頰黏膜纖維母細胞的增生率，但對正常 頰黏膜纖維母細胞較無細胞毒性。小孢子靈芝免疫調節蛋白處理可有效抑制纖維化 頰黏膜纖維母細胞膠體收縮力、細胞移動性、細胞侵襲性及傷口癒合能力。同時小 孢子靈芝免疫調節蛋白處理可減少檳榔素誘發正常頰黏膜纖維母細胞之肌纖維母細 胞特性如較高的細胞膠體收縮力、細胞移動性、細胞侵襲性及傷口癒合能力。小孢 子靈芝免疫調節蛋白亦可有效降低肌纖維母細胞相關標記(如COL1A1、α-SMA、FN 與vimentin)之mRNA 及蛋白質表現量。因此可藉由小孢子靈芝免疫調節蛋白去抑制 肌纖維母細胞的活性與相關分子訊號並開發為保健營養食品中的補充成分。
並列摘要
Oral submucous fibrosis (OSF) has been recognized as one of the oral potentially malignant disorders. Epidemiological studies have attributed this pathological fibrosis to the habit of areca nuts chewing, however, the detailed mechanism underlying the fibrogenesis and effective intervention still remain to be identified. Our previous works have found that the activation of myofibroblasts is associated with OSF. As such, exploring the natural compounds that inhibit myofibroblasts activities will be beneficial to the prevention and therapy of OSF and the following malignant transformation. In our preliminary studies, we have found that the proliferation ability of fibrotic buccal mucosal fibroblasts (fBMFs) decreased after exposure to GMI, an immunomodulatory protein from Ganoderma microsporum. And there was less cytoxicity in normal buccal mucosa fibroblasts. Treatment of GMI has shown to inhibit the collagen gel contraction, migration, and invasion abilities of fBMFs. Furthermore, we confirmed these findings in the arecoline-stimulated BMFs. Consistent with the above findings, the expression of the myofibroblast marker α-smooth muscle actin and other fibrogenic markers, such as type I collagen, fibronectin and vimentin in fBMFs were all reduced in a dose-dependent manner. Dietary supplement of GMI may serve as a good avenue to regulate myofibroblasts activities for OSF prevention.