The regulatory effects of transforming growth factor beta-activated kinase 1 on microglia pyroptosis in hypoxic-ischemic brain damage
10.3760/cma.j.issn.2096-2932.2022.01.015
- VernacularTitle:转化生长因子β激活激酶1对缺氧缺血性脑损伤中小胶质细胞焦亡的调控作用
- Author:
Yuan LYU
1
;
Weiwei HOU
;
Xingxing LU
;
Guihua SHU
;
Lingling ZHU
;
Yanyan CAI
Author Information
1. 扬州大学附属苏北人民医院（江苏省苏北人民医院）儿科 225000
- Keywords:
Hypoxia-ischemia, brain;
Pyroptosis;
Transforming growth factor beta-activated kinase1;
Microglia
- From:Chinese Journal of Neonatology
2022;37(1):65-69
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the regulatory effects of transforming growth factor beta-activated kinase 1 (TAK1) on microglia pyroptosis in hypoxic-ischemic brain damage (HIBD).Methods:Primary microglia cells were isolated from fetal mice and randomly assigned into 4 groups: the control group, 5z-7-oxozeaneol (5z-7) group, oxygen-glucose deprivation (OGD) group and OGD+5z-7 group. OGD models of microglia cells were established for the OGD groups and 5z-7 groups received a small molecule TAK1 inhibitor 5z-7. Expression of phosphorylated TAK1(P-TAK1), pyroptosis related proteins including NOD-like receptor pyrin domain containing 3 (NLRP-3), apoptosis-associated speck-like protein containing a CARD (ASC) oligomers, N terminal of Gasdermin D (GSDMD-N) and interleukin 1β (IL-1β) were examined using Western blot at 0 h, 6 h and 24 h after intervention. Lactate dehydrogenase (LDH) test and transmission electron microscope were used for pyroptosis evaluation.Results:(1) Compared with the control group, expressions of all proteins including P-TAK1, NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH level showed no significant differences in the OGD group at 0 h ( P>0.05). P-TAK1 levels in OGD group at 6 h and 24 h were lower than the control group and the levels of NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH were significantly higher ( P<0.05). Microglia pyroptosis (characterized by disruption of cell membrane, extravasation of cytoplasm and chromatin margin aggregation) was observed under electron microscope. (2) 5z-7 group and OGD+5z-7 group had lower P-TAK1 levels and higher NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH levels than the control group and OGD group at 6 h and 24 h. Conclusions:The down-regulation of TAK1 phosphorylation level may promote microglia pyroptosis in HIBD. This regulatory effects is related to the up-regulation of NLRP-3 expression and the oligomerization of ASC.
