RESUMEN
BACKGROUND/AIMS: WNT4 protein is important for kidney development. Its expression was found to be altered in experimental models of chronic kidney disease (CKD). However, the expression of the WNT4 gene has yet not been studied in human renal biopsy samples from patients with broad spectrum of glomerular disease and at different stages of CKD. Thus, the aim of the study was to assess the WNT4 gene expression in renal biopsies of 98 patients using the real-time PCR technique. MATERIALS: In order to assess the relative amounts of mRNA, in samples of patients with manifestation of different renal diseases and separately at different stages of CKD, by QPCR, total RNA was isolated from human kidney tissues collected during renal biopsies. Results of blood and urine samples assessment were used to calculate the correlations of biochemical parameters with WNT4 gene expression in both studied groups. RESULTS: After pathomorphological evaluation, 49 patients were selected as presenting the most common cases in the studied group. Among the patients who developed focal segmental glomerulosclerosis (FSGS; n = 13), IgA nephropathy (IgAN; n = 10), IgAN with morphological presentation of focal segmental glomerulosclerosis (IgAN/FSGS; n = 8), membranous nephropathy (MN; n = 12), and lupus nephritis (LN; n = 6) were included in the analysis. We found that the level of WNT4 mRNA was higher in kidney specimens obtained from patients with MN as compared to those diagnosed with LN or IgAN. A correlation between WNT4 gene expression and serum albumin and cholesterol levels was observed in patients with FSGS, while WNT4 mRNA levels correlated with plasma sodium in patients diagnosed with LN. After consideration of 98 patients, based on the KDIGO classification of CKD, 20 patients were classified as CKD1 stage, 23 as stage 2, 13 as stage 3a, 11 as stage 3b, 13 as stage 4, and 18 as stage 5. WNT4 gene expression was lower in the CKD patients in stage 2 as compared to CKD 3a. Correlations of WNT4 mRNA level at different stages of CKD with indices of kidney function and lipid metabolism such as serum levels of HDL and LDL cholesterol, TG, urea, creatinine, sodium, and potassium were also found. CONCLUSIONS: Our results suggest that altered WNT4 gene expression in patients with different types of glomerular diseases and patients at different stages of CKD may play a role in kidney tissue disorganization as well as disease development and progression.
Asunto(s)
Insuficiencia Renal Crónica/diagnóstico , Proteína Wnt4/genética , Adulto , Biopsia , Femenino , Humanos , Riñón/fisiopatología , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , Insuficiencia Renal Crónica/patología , Índice de Severidad de la Enfermedad , Proteína Wnt4/metabolismoRESUMEN
The contamination of plant material with mycotoxins, in particular of the genus Fusarium, is common in the natural environment. Multiparous female wild boars are exposed to feed contaminated with zearalenone (ZEN) and deoxynivalenol throughout the year. The aim of this study was to determine the concentrations of the above mycotoxins in multiparous female wild boars and to describe their effect on the histological structure of the ovaries at the beginning of astronomical winter. Toxicological examinations revealed 0.291 ng/ml of ZEN, 0.406 ng/ml of α-zearalenol (α-ZEL), 0.392 ng/ml ß-zearalenol (ß-ZEL) and an absence of deoxynivalenol (values below the sensitivity of the method) in the blood plasma of multiparous female wild boars. Numerous ovarian follicles at various stages of development, characterized by different degree of damage, were observed. Numerous deformed resting ovarian follicles were noted directly under the epithelium, and signs of follicular atresia and hyalinization were observed. Blood vessels in the medulla of the ovary were dilated, which probably improved the distribution of ZEN in the ovaries. Higher substrate (ZEN) concentrations in the ovaries led to an insignificant increase in the staining intensity of 3ß-HSD and 17ß-HSD clusters. The observed changes could contribute to prolonging the initial stage of late anestrus in multiparous female wild boars.