Mechanism of GLI1 mediated macrophages polarization in hypoxic pulmonary hypertension
10.3969/j.issn.1000-484X.2024.05.017
- VernacularTitle:GLI1介导的巨噬细胞极化调控缺氧性肺动脉高压的作用及机制
- Author:
Xiangrui ZHU
1
;
Jian MEI
;
Zhaosi WANG
;
Langlin OU
;
Lixin ZHANG
;
Xiaoying WANG
;
Siyu HE
;
Jun'e BAI
;
Xiaoyu GUAN
;
Hao YUAN
;
Cui MA
Author Information
1. 哈尔滨医科大学大庆校区医学检验与技术学院免疫教研室,大庆 163319
- Keywords:
Glioma-associated oncogene family zinc finger 1;
Hypoxia;
Macrophage;
M1 polarization;
Pulmonary hypertension
- From:
Chinese Journal of Immunology
2024;40(5):1016-1022
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore effect of Glioma-associated oncogene family zinc finger 1(GLI1)on hypoxia induced trans-formation of NR8383 to M1 phenotype and development of pulmonary hypertension(PH).Methods:Fifteen adult male Wistar rats were randomly divided into control group,hypoxia PH model group and hypoxic PH with GANT61 treatment group,with 5 rats in each group.PH related indexes of rats were detected by small animal ultrasound and right cardiac catheter experiment to determine effect of GLI1 specific inhibitor GANT61 on progression of PH.Pulmonary arterial thickness was measured by HE staining.α-SMA and M1 polarization markers TNF-α and IL-1β expressions were determined by immunohistochemistry.M1 polarization markers CD86 and TNF-α expressions were determined by immunofluorescence.GLI1 expression and NF-κB protein were detected by Western blot.mRNA expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 were detected by qRT-PCR.CHIP-PCR verified that GLI1 regulates NF-κB promoter activity.IL-12 content was detected by ELISA.Rat pulmonary artery smooth muscle cells proliferation was detected by CCK-8.Results:GLI1 inhibitor GANT61 could alleviate symptoms of PH in hypoxic rats(P<0.05).Compared with hypoxic group,inhibition of GLI1 reduced expressions of TNF-α and IL-1β in rat lung tissue(P<0.05).In cell experiments,hypoxia induced M1 polarization of NR8383 by up-regulating GLI1 to activate NF-κB pathway,GLI1 overexpression increased expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 in M1 macrophages(P<0.05).NR8383 culture supernatants could stimulate pulmonary artery smooth muscle cell proliferation(P<0.05)and contribute to development of PH.Conclusion:Hypoxia activates NF-κB pathway by up-regulating GLI1 to induce M1 polarization of macrophages contributes to development of PH.
