Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Biomed Res Int. 2020 Aug 2;2020:8035671. doi: 10.1155/2020/8035671. eCollection 2020.
To investigate the roles of ER stress in Kupffer cells (KCs) and KC-derived TNF- in the apoptosis of hepatic stellate cells (HSCs).
A rat model of liver fibrosis was established. Liver and blood serum samples were collected. Liver function assays, Masson staining, Sirius Red staining, ELISAs, and TUNEL and immunohistochemical staining were performed. Liver function, liver fibrosis, KC phenotype, inflammatory factors, and number of active HSCs were investigated. KCs were isolated, treated with tunicamycin, and then, cocultured with primary hepatic stellate cells. ELISAs, immunofluorescence staining, flow cytometry, and Western blotting were performed. KC phenotype, inflammatory factors, HSC apoptosis, and TNF-R1/caspase 8 pathway activity were examined.
s. ER stress in KCs reduced the levels of liver function markers, reduced the degree of liver fibrosis, and increased the number of KCs with the M1 phenotype and the expression of TNF-. The increase in KC-derived TNF- reduced the number of active HSCs and increased the activity of TNF-R1/caspase 8. Furthermore, ER stress in KCs promoted the polarization of KCs towards the M1 phenotype and increased the expression of TNF-. The increase in KC-derived TNF- triggered the apoptosis of HSCs and the activation of TNF-R1/caspase 8 in vitro, which was consistent with the in vivo results.
ER stress in KCs promotes the polarization of these cells towards the M1 phenotype and increases the expression of TNF-. Then, the increase in KC-derived TNF- triggers the apoptosis of HSCs through TNF-R1/caspase 8.
研究内质网应激（ER 应激）在枯否细胞（KCs）和 KC 来源的肿瘤坏死因子-α（TNF-α）在肝星状细胞（HSCs）凋亡中的作用。
建立大鼠肝纤维化模型。采集肝脏和血清样本。进行肝功能检测、Masson 染色、天狼猩红染色、ELISA、TUNEL 和免疫组织化学染色。研究肝功能、肝纤维化、KC 表型、炎症因子和活化 HSCs 的数量。分离 KCs，用衣霉素处理，然后与原代肝星状细胞共培养。进行 ELISA、免疫荧光染色、流式细胞术和 Western blot 分析。检测 KC 表型、炎症因子、HSC 凋亡和 TNF-R1/caspase 8 通路活性。
KC 中的 ER 应激降低了肝功能标志物的水平，减轻了肝纤维化的程度，并增加了 M1 表型的 KC 和 TNF-α的表达。增加的 KC 来源的 TNF-α减少了活化 HSCs 的数量，并增加了 TNF-R1/caspase 8 的活性。此外，KC 中的 ER 应激促进了 KC 向 M1 表型的极化，并增加了 TNF-α的表达。KC 来源的 TNF-α增加触发了 HSCs 的凋亡和 TNF-R1/caspase 8 的体外激活，这与体内结果一致。
KC 中的 ER 应激促进这些细胞向 M1 表型的极化，并增加 TNF-α的表达。然后，KC 来源的 TNF-α增加通过 TNF-R1/caspase 8 触发 HSCs 的凋亡。
