博碩士論文 106887604 詳細資訊



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姓名 Ying Dila(indira negari)  查詢紙本館藏   畢業系所 生醫科學與工程學系
論文名稱 益生菌活化表皮葡萄球菌透過FFaR2/p-ERK 信號傳導誘導膠原蛋白第I 型的產生
(Probiotic Activity of Staphylococcus epidermidis Induces Collagen Type I Production through FFaR2/p-ERK Signaling)
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摘要(中) 膠原蛋白第I型是由纖維細胞和細胞外基質所產生，是真皮組織的關鍵結構成分，皮膚老化過程是由內在或外在因素所引起的，例如自然老化或自由基暴露，會大大降低膠原蛋白的表達，從而導致皮膚彈性受阻。我們的研究以聚乙二醇 (PEG) 類似物鯨蠟硬脂基異壬酸酯 (CIN) 當作碳源讓皮膚表皮葡萄球菌 (S.epidermidis) 或丁酸發酵，它們的發酵代謝物可以恢復膠原蛋白。小鼠的纖維細胞和皮膚中的磷酸化細胞外信號調節激酶 (p-ERK) 活化。短鏈脂肪酸 (SCFA) 或游離脂肪酸受體 2 (FFaR2) 在體外和試管內實驗都顯著阻斷了表皮葡萄球菌對 p-ERK 誘導膠原蛋白的I型誘導的益生菌作用。這些結果表明發酵皮膚益生菌代謝產物中的丁酸 (BA) 通過 p-ERK 激活介導 FFaR2 誘導膠原蛋白的合成。我們在此認為以來自 CIN 當碳源可易使皮膚表皮葡萄球菌發酵的代謝物作為恢復真皮細胞外基質 (ECM) 中受損的膠原蛋白，為皮膚提供完整性和彈性。
摘要(英) Collagen type I is a key structural component of dermis tissue and is produced by fibroblasts and the extracellular matrix. The skin aging process, which is caused by intrinsic or extrinsic factors, such as natural aging or free radical exposure, greatly reduces collagen expression, thereby leading to obstructed skin elasticity. We investigated the effective fermentation of Cetearyl isononanoate (CIN), a polyethylene glycol (PEG) analog, as a carbon source with the skin probiotic bacterium Staphylococcus epidermidis (S. epidermidis) or butyrate, as their fermentation metabolites could noticeably restore collagen expression through phosphorylated extracellular signal regulated kinase (p-ERK) activation in mouse fibroblast cells and skin. Both the in vitro and in vivo knockdown of short-chain fatty acid (SCFA) or free fatty acid receptor 2 (FFaR2) considerably blocked the probiotic effect of S. epidermidis on p-ERK-induced collagen type I induction. These results demonstrate that butyric acid (BA) in the metabolites of fermenting skin probiotic bacteria mediates FFaR2 to induce the synthesis of collagen through p-ERK activation. We hereby imply that metabolites from the probiotic S. epidermidis fermentation of CIN as a potential carbon source could restore impaired collagen in the dermal extracellular matrix (ECM), providing integrity and elasticity to skin.
關鍵字(中) ★ 丁酸
★ 膠原蛋白第I型
★ 益生菌
★ 葡萄球菌		 關鍵字(英) ★ butyric acid
★ collagen type I
★ probiotic
★ Staphylococcus epidermidis
論文目次 Abstract i
Acknowledgments iii
Publication arising during PhD candidature iv
Table of Contents v
List of Figures vi
List of Tables vi
Explanation of Symbols and Abbreviations vii
Chapter I. Introduction 1
1.1. Background of research study 1
1.2. Probiotic 2
1.3. Normal skin function 2
1.4. Dermal extracellular matrix 3
1.5. Staphylococcus epidermidis and its benefit for skin microbiome 5
1.6. The bacterial pathways of anaerobic SCFA production 7
1.7. Selective fermentation initiator (SFI) 10
1.8. The FFaR2 receptor of SCFA 13
1.9. Research objectives 16
Chapter II. Methods 17
2.1. Bacterial culture 17
2.2. Fermentation of bacteria 17
2.3. GC‐MS analysis 17
2.4. Cell culture 17
2.5. Western-blotting 18
2.6. siRNA-mediated gene silencing of GPR43/FFaR2 19
2.7. Drug treatment 19
2.8. qPCR 19
2.9. Statistical analysis 20
Chapter III. Results 22
3.1. CIN as a selective fermentation initiators (SFIs) for S. Epidermidis 22
3.2. Mixture of CIN and S. epidermidis induces the expression of collagen type I and p-ERK production in mouse skin 24
3.3. Knocking down FFaR2 inhibited BA mediated induction of collagen type I and p-ERK in mouse fibroblast 25
3.4. Knocking down FFaR2 inhibited fermentation metabolite mediated induction of collagen type I and p-ERK in mouse skin 28
Chapter IV. Discussion 32
4.1. General discussion 25
4.2. Limitations and future works 28
Chapter V. Conclusion 38
References…………………………………………………………………………………......... 39
List of Figures
Fig. 1. Schematic overview of the three pathways 9
Fig. 2. S. epidermidis mediates triggers CIN fermentation to produce SCFAs…………………22
Fig. 3. Application of mixture of S. epidermidis and CIN induces collagen type I and p-ERK expression in mouse skin. 24
Fig. 4. Blocking FFaR2 prevents the BA mediated collagen type I and p-ERK induction 26
Fig. 5. Blocking FFAR2 prevents the butyric acid mediated collagen and phosphorylated ERK induction 287
Fig. 6. Blocking FFAR2 prevents the fermentation mediated collagen induction in NIH 3T3 cells 27
Fig. 7. Blocking FFaR2 prevents the fermentation mediated collagen type I and p-ERK induction in mouse skin model. 28
Fig. 8. Blocking FFAR2 prevents the fermentation mediated collagen induction in mouse skin model 29
Fig. 9. Induction of collagen content by application of BA 30
Fig. 10. Blocking FFaR2 mediated collagen induction by BA in mouse skin model 30
Fig. 11. Conclusion model of the mechanism how S. epidermidis produce SCFAs 38

List of Table
Table 1. List of compounds detected by GC-MS tation to produce SCFAs 23
Table 2. List of differences between the three carbon sources 23
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指導教授 Wang Sunchong Lee Yuhsiang Chen Chingyun Huang Weihsing Hsieh Mingfang Hwang Tzannshun(Sun-Chong Wang Yu-Hsiang Lee Ching-Yun Chen Wei-Hsing Huang Ming-Fang Hsieh Tzann-Shun Hwang) 審核日期 2022-7-11
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