Formation of vitamin A lipid droplets in pancreatic stellate cells requires albumin
Formation of vitamin A lipid droplets in pancreatic stellate cells requires albumin
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DOI：
10.1136/gut.2008.170233
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发表时间：
2009-10-01
期刊：
影响因子：
24.5
通讯作者：
Oh, J.
中科院分区：
文献类型：
--
作者：
Kim, N.;Yoo, W.;Oh, J.
目的：静止的胰腺星状细胞（PSC）以细胞质脂滴的形式储存维生素A，并且当被促纤维化刺激激活时，它们转化成肌纤维母细胞样细胞，其特征在于维生素A液滴的损失。星状细胞的活化是纤维形成的核心，但维生素A液滴的形成机制及其与星状细胞活化的关系尚不清楚。方法：利用培养的PSC，尝试验证星状细胞内源性表达的白蛋白的功能。白蛋白在静止PSC中内源性表达，定位于细胞质脂滴中，并且其水平在星状细胞活化后显著降低。即使在细胞传代后，星状细胞中持续的白蛋白表达也足以维持其脂肪储存表型，并使细胞对转化生长因子β（TGF β）的活化作用具有抗性。第2代后PSC中白蛋白的强制表达（活化的PSC）诱导脂滴的重新出现和表型变化，这是先前用视黄醇治疗报告的。视黄醇增加白蛋白的合成在激活的PSC和白蛋白的表达抑制使用小干扰RNA（siRNA）废除视黄醇诱导的effects.Conclusions：数据表明白蛋白在星状细胞的细胞质维生素A脂滴的形成中的一种新的作用，并表明白蛋白可能有一个直接的影响星状细胞活化。
Objective: Quiescent pancreatic stellate cells (PSCs) store vitamin A as cytoplasmic lipid droplets, and, when activated by profibrogenic stimuli, they transform into myofibroblast-like cells characterised by the loss of vitamin A droplets. Activation of stellate cells is central to fibrogenesis, but the mechanism for the formation of vitamin A droplets and its relationship to stellate cell activation remain unclear.Methods: With use of cultured PSCs, an attempt was made to characterise the function of albumin endogenously expressed in stellate cells.Results: Albumin is endogenously expressed in quiescent PSCs, localised in cytoplasmic lipid droplets, and its levels are markedly reduced after stellate cell activation. Continuous albumin expression in stellate cells is sufficient to maintain their fat-storing phenotype even after cell passages and renders cells resistant to the activating effects of transforming growth factor beta (TGF beta). Forced expression of albumin in PSCs after passage 2 (activated PSCs) induced the re-appearance of lipid droplets and phenotypic changes, which were previously reported with retinol treatment. Retinol increases albumin synthesis in activated PSCs and the suppression of albumin expression using small interfering RNA (siRNA) abolishes retinol-induced effects.Conclusions: The data demonstrate a novel role for albumin in the formation of cytoplasmic vitamin A lipid droplets in stellate cells, and suggest that albumin may have a direct influence on stellate cell activation.