ABSTRACT
Steroid-resistant nephrotic syndrome (SRNS) is a relatively difficult clinical type of treatment.The major therapy measures in present include steroid and immunosuppressant.Commonly used immunosuppressant include tacrolimus,cyclosporin,cyclophosphamide,mycophenolate mofetil,ect.Tacrolimus-induced clinical remission rate is superior to other immunosuppressive agents,has been the first-line agent of SRNS.Because of the individual difference in metabolism,the drug concentration of tacrolimus should be determined periodically.In order to obtain optimal efficacy of tacrolimus and reduce renal toxicity,the treatment protocols of small doses with long courses for children with SRNS were recommended.
ABSTRACT
microRNAs play an important regulative role in body's growth and development,and the development of the disease process.Much microRNAs can maintain normal kidney function and regulate kidney pathological process,the miR-30a has extensive effect on kidney development and progression of renal diseases.In this review,a brief overview on the role of miR-30a in renal pathology is presented.
ABSTRACT
Objective Few researches have been reported on the gene methylation in children with steroid-sensitive nephrot-ic syndrome (SSNS) or steroid-dependent nephrotic syndrome (SDNS).This study aimed to investigate the possible pathogenesis and therapeutic target of SSNS and SDNS by screening differentially methylated genes ( DMGs) and bioinformatic analysis using DNA meth-ylation microarray. Methods This study included 3 hospitalized children with SSNS and another 4 with SDNS, all treated with full dose of prednisone ( 2 mg per kilogram of the body weight per day or 60 mg per m2 per day).Negative urine protein was achieved within 4 weeks in the former group , while the latter , though sensitive to hor-monal therapy , relapsed within 2 weeks after drug withdrawal or dose reduction .DNA was extracted from the peripheral blood of the patients in both groups for screening DMGs and bioinformatic analysis using DNA methylation microarray . Results Compared with the patients with SSNS, 318 DMGs were found in the SDNS group , among which 193 were hypermethylated and the other 125 hypomethylated .These abnormal genes were mainly located in the open reading frame of DNA and the CpG island region .DMGs were mainly involved in Rho guanyl-nucleotide exchange factor activity , nucleoside-triphosphatase regulator activity , GTPase activator activity , and other molecular functions .The biological processes were chiefly associ-ated with the regulation of the generation of precursor metabolites and energy , antigen processing and presentation , regulation of Rho and Ras protein signal transduction , lamellipodium assembly , regeneration , and other biological processes .The cell composition was mainly related to MHC protein complexes , perichromatin fibrils , and the MHC class I protein complex .Analysis of the KEGG signaling pathway showed that DMGs participated in 9 signaling pathways , involving type I diabetes , starch and sucrose metabolism , allograft re-jection, autoimmune thyroid disease , and others. Conclusion The heterogeneity of methylation is widespread in children with SDNS and may be one of the causes of steroid dependence , which has provided a basis for searching for potential therapeutic targets .
ABSTRACT
Objective Through selecting abnormal DNA methylation of children steroid resistance nephrotic syndrome and bioinformatics analysis to find the pathogenesis of steroid resistance nephrotic syndrome and provide new targets for therapy. Methods We use illumine 450K methylation chip to detected blood gene DNA methylation of 9 cases of children primary nephrotic syndrome. 9 cases were divided into 2 groups: G1 is the group of steroid sensitive nephritic syndrome, a total of 4 cases; G2 is the group of steroid resistance nephrotic syndrome, a total of 5 cases. Selected the abnormal DNA methylation in children steroid resistant nephritic syndrome, clarified the function of those genes through using functional annotation of gene GO, enrichment analysis and KEGG pathway analysis, conducted the preliminary analysis on children with steroid resistant nephrotic syndrome of gene methylation. Results Compared with the control group, G2 has a number of genes that were extensively methylated. According to the results of bioinformatics analysis, the abnormal DNA methylation in G2 is the components of the various kinds of organelles and cell membrane. They also regulated the polymerization and composition of cytoskeleton and actin, as well as involved in the process of metabolism of many amino acids and drug. Conclusions The abnormal DNA methylation in the group 2 have extensive role, offering possibility of clinical prediction and provided potential therapeutic targets.