Differential expression of transfer RNA-derived small RNAs in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. Recent studies have indicated that small noncoding RNAs, such as tRNA-derived small RNAs (tsRNAs), might be novel biomarkers for glomerulonephritis. We therefore investigated the potential roles and possible functions of the tsRNAs in IgAN. METHOD: Peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of the patients with IgAN and healthy control groups. The expression profiles of tsRNAs were assessed by small RNA sequencing (RNA-Seq) in PBMCs of the IgAN and control groups. Dysregulated tsRNAs were selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). Target gene prediction and enrichment were performed by bioinformatics analysis. RESULTS: The results revealed that 143 significantly upregulated and 202 significantly downregulated tsRNAs were differentially altered in the IgAN group compared with the control group. Five upregulated tsRNAs (tRF-Val-AAC-007, tRF-Ala-AGC-063, tRF-Gln-CTG-010, tRF-Tyr-GTA-011 and tRF-Thr-AGT-007) and 3 downregulated tsRNAs (tiRNA-Val-TAC-004, tRF-Gly-CCC-005 and tRF-His-GTG-006) were selected for validation by qRT-PCR; the results were consistent with the sequencing data. Gene Ontology (GO) analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in "nucleic acid metabolic process,' "intracellular part,' and "ion binding,' whereas the target genes predicted by downregulated tsRNAs were mostly enriched in "regulation of cellular component organization,' "membrane-bound organelle,' and "ion binding.' Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in "herpes simplex virus 1 infection,' whereas the target genes predicted by downregulated tsRNAs were mostly enriched in "circadian rhythm CONCLUSIONS:: The present study confirmed the differential expression of tsRNAs in patients with IgAN, and these dysregulated tsRNAs might be novel potential targets for the diagnosis and treatment of IgAN.

Relationship between Renalase Expression and Kidney Disease: an Observational Study in 72 Patients Undergoing Renal Biopsy.

The relationship between the levels of renalase and changes in proteinuria, hypertension, renal function, renal tubular epithelial cell apoptosis and B-cell lymphoma-2 (Bcl-2) expression was investigated in patients (chronic nephritis, primary nephrotic syndrome or other kidney disease) that underwent renal biopsy. The study group comprised 72 patients undergoing renal biopsy. Patient profiles and renal function were collected. Concentrations of renalase and Bcl-2 were measured by immunohistochemistry. Tubular injury was detected by periodic acid Schiff staining (PAS) and renal tubular epithelial cell apoptosis was assessed by TUNEL assay. The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues. There was a positive linear relationship between renalase and some serum and cardiac indices; a negative correlation was found between age, eGFR, Ccr and 24-h urinary protein. Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase. The results showed that renalase probably increased the expression of Bcl-2. By two independent samples t-test, renalase levels were significantly increased in the non-hypertension group than in the hypertension group. One-way ANOVA showed that renalase expression was higher in samples with Lee's grade III than in those with Lee's grade V. The expression of renalase was significantly decreased in patients who underwent renal biopsy, and was also associated with blood and renal function. The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway, finally achieving the purpose of delaying the progress of renal failure.

[Effect of Astragalus mongholicus on renal gene expression profile in mice with diabetic nephropathy].

OBJECTIVE: To study the effect of Astragalus mongholicus on renal gene expression profile in mice with diabetic nephropathy by cDNA microarray. METHOD: The mice with diabetic nephropathy were fed A. mongholicus and normal saline respectively. cDNA microarray was used to measure gene expression profile in renal tissue after 12 weeks, and the data were analyzed by bioinformatics. RT-PCR was performed to detect the relative levels of some genes which were randomly selected. RESULT: Eighty eight genes were found differently expressed in two chips. Among these genes, 81 genes were found differently expressed in reverse direction change, 7 genes were found differently expressed in same direction change. The genes altered were mainly related to material metabolism, immunity and inflammatory reaction, signal transduction, translation, transcription, et al. The expressions of genes tested by RT-PCR were in accordance with those detected by cDNA microarray. CONCLUSION: A. mongholicus may play protective roles in diabetic nephropathy through multiple pathways at gene level. The effect of A. mongholicus in genes related to material metabolism is more significant.

The structural and hormonal basis of sex differences in peak appendicular bone strength in rats.

To identify the structural and hormonal basis for the lower incidence of fractures in males than females, sex differences in femoral mid-shaft geometry and breaking strength were studied in growth hormone (GH)-replete and -deficient male and female rats. Sexual dimorphism appeared during growth. Cortical thickening occurred almost entirely by acquisition of bone on the outer (periosteal) surface in males and mainly on the inner (endocortical) surface in females. By 8 months of age, males had 22% greater bone width and 33% greater breaking strength than females. Gonadectomy (Gx) at 6 weeks reduced sex differences in bone width to 7% and strength to 21% by halving periosteal bone formation in males and doubling it in females. Gx had no net effect on the endocortical surface in males but abolished endocortical bone acquisition in females. GH deficiency halved periosteal bone formation and had no net effect on the endocortical surface in males, but abolished bone acquisition on both surfaces in females, leaving males with 17% greater bone width and 44% greater breaking strength than females. Sex hormone deficiency produces greater bone fragility in males than females by removing a stimulator of periosteal growth in males and removing an inhibitor of periosteal growth in females. GH deficiency produces less bone fragility in males than females because males retain androgen-dependent periosteal bone formation while bone acquisition on both surfaces is abolished in females. Thus, periosteal growth is independently and additively stimulated by androgens and GH in males, inhibited by estrogen, and stimulated by GH in females. The hormonal regulation of bone surfaces establishes the amount and spatial distribution of bone and so the sexual dimorphism in its strength.