Effects of Glucocorticoid-Induced Transcript 1 Gene Deficiency on Glucocorticoid Activation in Asthmatic Mice / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 2817-2826, 2018.
Article
in English
| WPRIM
| ID: wpr-772916
ABSTRACT
Background@#Glucocorticoid (GC) is the first-line therapy for asthma, but some asthmatics are insensitive to it. Glucocorticoid-induced transcript 1 gene (GLCCI1) is reported to be associated with GCs efficiency in asthmatics, while its exact mechanism remains unknown.@*Methods@#A total of 30 asthmatic patients received fluticasone propionate for 12 weeks. Forced expiratory volume in 1 s (FEV) and GLCCI1 expression were detected. Asthma model was constructed in wild-type and GLCCI1 knockout (GLCCI1) mice. Glucocorticoid receptor (GR) and mitogen-activated protein kinase phosphatase 1 (MKP-1) expression were detected by polymerase chain reaction and Western blotting (WB). The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also detected by WB.@*Results@#In asthmatic patients, the change of FEV was well positively correlated with change of GLCCI1 expression (r = 0.430, P = 0.022). In animal experiment, GR and MKP-1 mRNA levels were significantly decreased in asthmatic mice than in control mice (wild-type GR 0.769 vs. 1.000, P = 0.022; MKP-1 0.493 vs. 1.000, P < 0.001. GLCCI1 GR 0.629 vs. 1.645, P < 0.001; MKP-1 0.377 vs. 2.146, P < 0.001). Hydroprednisone treatment significantly increased GR and MKP-1 mRNA expression levels than in asthmatic groups; however, GLCCI1 asthmatic mice had less improvement (wild-type GR 1.517 vs. 0.769, P = 0.023; MKP-1 1.036 vs. 0.493, P = 0.003. GLCCI1 GR 0.846 vs. 0.629, P = 0.116; MKP-1 0.475 vs. 0.377, P = 0.388). GLCCI1 asthmatic mice had more obvious phosphorylation of p38 MAPK than wild-type asthmatic mice (9.060 vs. 3.484, P < 0.001). It was still higher even though after hydroprednisone treatment (6.440 vs. 2.630, P < 0.001).@*Conclusions@#GLCCI1 deficiency in asthmatic mice inhibits the activation of GR and MKP-1 and leads to more obvious phosphorylation of p38 MAPK, leading to a decremental sensitivity to GCs.@*Trial Registration@#ChiCTR.org.cn, ChiCTR-RCC-13003634; http//www.chictr.org.cn/showproj.aspx?proj=5926.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Physiology
/
Asthma
/
Receptors, Glucocorticoid
/
Forced Expiratory Volume
/
Mice, Knockout
/
Therapeutic Uses
/
P38 Mitogen-Activated Protein Kinases
/
Drug Therapy
/
Dual Specificity Phosphatase 1
Limits:
Animals
Language:
English
Journal:
Chinese Medical Journal
Year:
2018
Type:
Article
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