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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Title:	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
Authors:	Dila, Ying;negari, indira
Contributors:	生醫科學與工程學系
Keywords:	丁酸;膠原蛋白第I型;益生菌;葡萄球菌;butyric acid;collagen type I;probiotic;Staphylococcus epidermidis
Date:	2022-07-11
Issue Date:	2022-10-04 11:08:57 (UTC+8)
Publisher:	國立中央大學
Abstract:	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。 ;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.
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