TSG-6 secreted by human adipose tissue-derived mesenchymal stem cells ameliorates severe acute pancreatitis via ER stress downregulation in mice.
TSG-6 secreted by human adipose tissue-derived mesenchymal stem cells ameliorates severe acute pancreatitis via ER stress downregulation in mice.
复制标题
DOI：
10.1186/s13287-018-1009-8
复制
发表时间：
2018-09-26
影响因子：
7.5
通讯作者：
Youn HY
中科院分区：
文献类型：
--
作者：
Li Q;Song WJ;Ryu MO;Nam A;An JH;Ahn JO;Bhang DH;Jung YC;Youn HY
通过最近的研究，揭示了胰腺腺泡细胞（PAC）中急性胰腺炎的发病以及PAC在重症急性胰腺炎（SAP）中的调节作用。在胰腺炎的早期阶段，PAC 中的内质网 (ER) 发生显着变化，包括肿胀和空泡化。为了应对 ER 细胞外应激的增加，PAC 失去其功能，导致细胞凋亡和炎症反应。人类脂肪组织来源的间充质干细胞 (hAT-MSC) 对 SAP 的有益作用已在之前的研究中得到充分证明。然而，其作用的根本机制仍然存在争议。在本研究中，评估了腹腔注射 hAT-MSC 在雨蛙素 (50 μg/kg) 和脂多糖 (LPS) (10 mg/kg) 共同诱导的 SAP 小鼠模型中的治疗效果。在胰腺组织样本中测量炎症反应和内质网应激，并通过定量逆转录聚合酶链反应（qRT-PCR）、蛋白质印迹和免疫荧光分析评估有益效果。 hAT-MSC 注射后炎症反应和 ER 应激得到改善，并且在 hAT-MSC 没有明显植入的情况下观察到有益效果。转染 siRNA 靶向肿瘤坏死因子-α 诱导基因/蛋白 6 (TSG-6) 的 hAT-MSC 无法抑制 ER 应激和炎症。此外，来自 hAT-MSC 的 TSG-6 显着抑制 SAP 模型小鼠中 ER 应激诱导的细胞凋亡和核因子 kappa B (NF-κB) 活性。 hAT-MSC 分泌的 TSG-6 通过抑制 ER 应激和炎症反应来保护 SAP 模型小鼠的 PAC。这项研究揭示了 SAP 患者 ER 应激靶向治疗的新领域。本文的在线版本 (10.1186/s13287-018-1009-8) 包含补充材料，可供授权用户使用。
Through recent studies, the onset of acute pancreatitis in pancreatic acinar cells (PACs) and the regulatory role of PACs in severe acute pancreatitis (SAP) have been revealed. During the early stages of pancreatitis, the endoplasmic reticulum (ER) in PACs undergoes significant changes, including swelling and vacuolization. In response to an increase in the extracellular stress in ER, PACs lose their functions, leading to cell apoptosis and inflammation response. The beneficial effects of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) on SAP have been well documented in previous studies. However, the underlying mechanism of their action remains controversial. In this study, the therapeutic effects of intraperitoneally administered hAT-MSCs in a caerulein (50 μg/kg)- and lipopolysaccharide (LPS) (10 mg/kg)-co-induced SAP mouse model were evaluated. Inflammatory response and ER stress were measured in pancreatic tissue samples, and the beneficial effects were evaluated through quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence analysis. Inflammatory response and ER stress were ameliorated following hAT-MSC injection, and the beneficial effects were observed in the absence of significant engraftment of hAT-MSCs. hAT-MSCs transfected with siRNA-targeting tumour necrosis factor-α-induced gene/protein 6 (TSG-6) were unable to inhibit ER stress and inflammation. In addition, TSG-6 from hAT-MSCs significantly suppressed ER stress-induced apoptosis and nuclear factor kappa B (NF-κB) activity in SAP model mice. TSG-6 secreted by hAT-MSCs protects PACs in SAP model mice via the inhibition of ER stress, as well as inflammatory responses. This study has revealed a new area for ER stress-targeted therapy in SAP patients. The online version of this article (10.1186/s13287-018-1009-8) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
29
作者：
Baker RG;Hayden MS;Ghosh S
通讯作者：
Ghosh S
影响因子：
3.1
作者：
ADLER, G;ROHR, G;KERN, HF
通讯作者：
KERN, HF
影响因子：
5.2
作者：
Kim, Hyung-Sik;Yun, Jun-Won;Kang, Kyung-Sun
通讯作者：
Kang, Kyung-Sun
影响因子：
7.5
作者：
Bazhanov N;Ylostalo JH;Bartosh TJ;Tiblow A;Mohammadipoor A;Foskett A;Prockop DJ
通讯作者：
Prockop DJ
静脉注射HMSC改善了小鼠的心肌梗塞，因为栓塞在肺中的细胞被激活以分泌抗炎蛋白TSG-6。
影响因子：
23.9
作者：
Lee RH;Pulin AA;Seo MJ;Kota DJ;Ylostalo J;Larson BL;Semprun-Prieto L;Delafontaine P;Prockop DJ
通讯作者：
Prockop DJ