| Objective: Myasthenia gravis (MG) is one kind of autoimmune disease (AID) which is treated mainly and effectually by Glucocorticoid (GC) in mang treatments. Studies suggest that the effect of GC are mediated by high affinity with the combination of GR, GRis a key for GC to play its physiological and pharmacology effects. the content of GR directly affect the body's response to GC. Heat shock protein 90 (HSP90) is an important chaperonin of GR. In order to further explore the relationship between glucocorticoid receptor,HSP90α,βand glucocorticoid sensitivity ,we investigated the expression of GRα,GRβ,HSP90α,HSP90βand its interaction in children with MG pre or post GC treatment in myasthenia gravis GC sensitive group ,GC dependent group and GC resistant group with myasthenia gravis.Methods: The children with MG were enrolled in this study, which were divided as GC sensitive group (SS, 19 cases), GC dependence group (SD, 3 cases). Meanwhile, the same age of children as the normal control (17 cases). The periphery blood (PB) was collected from above-mentioned children. Part of the PB was isolated the mononeuclear cells and mRNA for detecting the gene expression of GRα, GRβ, HSP90αand HSP90βwith RT-PCR, the other part of the cells were used to test these proteins'expression with immunocytochemical assay (ICC).Results:1. Both the mRNA and protein expression of GRαand GRβin children in GC sensitive group and GC dependent group are higher than children in normal group before GC treatment(P<0.05). And there was no statistical difference between children in GC sensitive group and GC dependent group(P>0.05).After GC treatment, both the mRNA and protein expression of GRα,GRβin children with GC sensitive group, the GRαexpression in children with GC dependent group resumed normol. However, the expression of GRβin children with dependent group is higher than that of normal group(P<0.05). After GC treatment, both the mRNA and protein expression of GRαand GRβwere decreased in children with GC sensitive group. There was statistical difference between GRβexpression in children with pre-GC treatment and post- GC treatmen(tP<0.05).However, there was no statistical difference in the expression of GRαand GRβin children with GC dependent group between pre-GC treatment and post- GC treatment(P>0.05).2. Both the mRNA and protein expression of HSPαand HSPβin children with GC sensitive group and GC dependent group were higher than children in normal group before GC treatment(P<0.05). However, there was no statistical difference between children with GC sensitive group and dependent group(P>0.05).After GC treatment , the mRNA and protein expression of HSPαin children with GC sensitive group and dependent group is still higher than that of normol group(P<0.05). The HSPβexpression in children with GC sensitive group resumed normal.However, HSPβexpression was still higher in children with GC dependent group than that of normal group(P<0.05); In GC sensitive group, both the mRNA and protein expression of HSPαand HSPβwere decreased. There was no statistical difference between pre-GC treatment and post- GC treatment(P>0.05). In GC dependent group ,there was no difference in GRαand GRβexpression between pre-GC treatment and post- GC treatment(P>0.05).Conclusion:1.Most myasthenia gravis children patients are sensitive to glucocorticoid treatment. In this study, no resistant patient was found and only 3 patients was GC dependent (13.6%).2.Both the mRNA and protein expression of GRαand GRβin GC sensitive group and GC dependent group were higher than children in normal group in pre-GC treatment,we deduce that there are some relationship between pathogenesis of myasthenia gravis and high GRαand GRβexpression. And the high GRαexpression was related to its delayed transit or abnormal function. The high GRβexpression probably inhibit GC transiting into the nucleus and then playing its pharmacological effect carried by GC. After GC treatment, the expression of GRαand GRβin GC sensitive group and GRαexpression in GC dependent group resumed normol. However, GRβexpression in GC dependent group is higher than that of normal group. Meanwhile, GRβexpression was decreased in GC sensitive group after GC treatment, but GRβexpression was still higher in GC dependent group than that of normal group. Therefore, we think that the high GRβexpression could inhibit or reduce the GRa activation role of target gene, which might affect GC in gene regulation.3. Both the expression of HSPαand HSPβwere higher than children in GC sensitive and dependent group than that in normal group. So, we expected that children with MG were in stress, the high HSP90 expression is related to stress, increased inflammation and other pathological conditions. The increased HSP90expression may affect GR's function and the physiological effects of GC. HSPβexpression in pre-GC treatment and post- GC treatment is no difference between GC sensitive group and normal group,yet it is higher of HSP90βexpression in GC dependent group than that in normal group, so we considered that HSP90βmay cause difficult in combination between GR and GC or in dissociation between GR and HSP90. Therefore, GR could not combine with GC effectively, and thus affect GC regulating gene transcription , which result in children of GC dependence.
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