Antifibrotic Effect of Saturated Fatty Acids via Endoplasmic Reticulum Stress Response in Rat Pancreatic Stellate Cells.
Antifibrotic Effect of Saturated Fatty Acids via Endoplasmic Reticulum Stress Response in Rat Pancreatic Stellate Cells.
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DOI：
10.1097/mpa.0000000000000757
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发表时间：
2017-03
期刊：
影响因子：
2.9
通讯作者：
Takayanagi R
中科院分区：
文献类型：
--
作者：
Lee L;Ito T;Nakamura T;Jensen RT;Igarashi H;Takayanagi R
通过对胰腺纤维化的主要效应细胞--胰星状细胞(PSCs)内质网(ER)应激反应的研究，探讨饱和脂肪酸在CP发病中的作用。将Wistar Bonn/Kobori(KOB)大鼠分为对照组和高脂饲料(HFD)组，饲养4周。同时，用内质网应激诱导剂thapsigargin(TG)或棕榈酸(PA)刺激培养的大鼠PSCs。检测胰腺纤维化、纤维化相关蛋白和内质网应激相关蛋白及mRNA的表达、细胞存活率和细胞凋亡率。高脂饲料可减少幼年高脂饲料喂养的大鼠胰腺纤维化和α-平滑肌肌动蛋白的表达(即激活的PSC)，但上调ER应激相关基因的表达。TG或PA诱导PSCs的内质网应激反应诱导细胞凋亡，激活PERK通路，抑制细胞活力，下调纤维化相关蛋白和mRNA的表达。PERK抑制剂可阻断PA诱导的内质网应激反应。至少在早期，饱和脂肪酸可以通过PSCs中的内质网应激反应(即PERK途径)抑制但可能不促进CP的纤维化形成。此外，在PSCs中诱导凋亡的内质网应激反应可能是治疗胰腺纤维化的一种新策略。
We investigated the effect of saturated fatty acids on the CP pathogenesis by elucidating the endoplasmic reticulum (ER) stress response in pancreatic stellate cells (PSCs), which are major effector cells in pancreatic fibrosis. Wistar Bonn/Kobori (KOB) rats were fed either control diet or high-fat diet (HFD) for 4 weeks. Meanwhile, cultured rat PSCs were stimulated with thapsigargin (Tg), an ER stress inducer, or palmitic acid (PA). Pancreatic fibrosis, expressions of fibrosis-related and ER stress-related proteins and mRNA, cell viability and apoptosis were examined. HFD reduced fibrosis and α-smooth muscle actin expression (i.e., activated PSCs) but upregulated ER stress-related mRNA expression in the pancreas of young HFD-fed KOB rats. Induction of ER stress response in PSCs with Tg or PA induced apoptosis, activated the PERK pathway, inhibited cell viability, and downregulated fibrosis-related protein and mRNA expression. PERK inhibitor negated PA-induced ER stress response. Saturated fatty acids can inhibit but may not promote the fibrogenesis of CP, at least in the early stage, via an ER stress response (i.e., the PERK pathway) in PSCs. Moreover, induction of an apoptotic ER stress response in PSCs might be a novel therapeutic strategy for pancreatic fibrosis.