Effects of Acetylated Glucocorticoid Receptor and Histone 3/Histone 4 on Glucocorticoid Response in Children Patients with Primary Nephrotic Syndrome

Abstract

Abstract Introduction : Glucocorticoid (GC) response resistance is considered a poor prognostic indicator but the mechanism of the resistance remains unknown. We explored the possible reasons from an epigenetic perspective. Methods The glucocorticoid receptor protein expression and acetylated GC receptor (Ac-GR) as well as acetylated histone3(Ac-H3), histone4 (Ac-H4) and the activity of nuclear factor-κB (NF-κB) were measured in peripheral blood lymphocytes of patients with different GC response. Results Before GC treatment, the Ac-GR, Ac-H3, Ac-H4 and NF-κB were lowly expressed in the control children and were highly expressed in the steroid-resistant nephrotic syndrome (SRNS) children, while moderately expressed in the steroid-sensitive nephrotic syndrome (SSNS) children. After GC treatment, expressions of Ac-GR, Ac-H3, Ac-H4 and NF-κB decreased in the SSNS children, while increased in the SRNS children. The correlations between Ac-GR, Ac-H3, Ac-H4 and NF-κB were remarkably distinct between the SSNS and SRNS groups. A positive correlation between NF-κB and Ac-GR after the GC treatment was found in the SSNS group. A positive correlation for the difference was observed between Ac-H3 and Ac-H4 in the SSNS group, whereas this correlation was not seen in the SRNS group. Conclusion Ac-GR, Ac-H3 and Ac-H4 were differentially expressed in primary nephrotic syndrome (PNS) children with different GC responses; the acetylation of GR, H3 and H4 may be influenced by GC administration directly.