Changes in renal WT-1 expression preceding hypertension development

Abstract

BackgroundHypertension is a public health problem with mostly unknown causes, and where strong hereditary genetic alterations have not been fully elucidated. However, the use of experimental models has provided valuable information. Recent evidences suggest that alterations in key nephrogenic factors, such as Wilms’ tumor 1 transcription factor (WT-1), could contribute to the development of hypertension. The aim of this paper is to evaluate the expression of WT-1 and related genes in the nephrogenic process in connection with the development of hypertension as well as the corresponding anatomical and functional correlation.MethodsMale spontaneously hypertensive and control rats were evaluated weekly from birth until week 8 of life. Their blood pressure was taken weekly using the tail-cuff blood pressure system. Weekly, 5 rats per group were sacrificed with a lethal injection of pentobarbital, and their kidneys were removed, decapsulated and weighed. The serum was collected for measuring biochemical parameters. The results were assessed using one-way analysis of variance for comparisons between groups.ResultsThe relationship between renal weight/total body weights was established, without significantly different values. These data were compared with apoptosis, fibrosis, number and size of the glomeruli. The elevation of systolic blood pressure was significant since week 6. Biochemical values differed slightly. Histology showed a slight increase in deposits of collagen fibers since week 4. Additionally, in kidney cortices, the expression of WT-1, heat shock protein 70 (Hsp70) and vitamin D receptors (VDR) decreased since week 4. Finally, we demonstrated ultrastructural damage to mitochondria since week 4.ConclusionsOur results would suggest an unprecedented link, possibly a regulatory mechanism, between WT-1 on nephrogenic alteration processes and their relationship with hypertension. Moreover, and previous to the increase in blood pressure, we demonstrated low expressions of WT-1, VDR and Hsp70 in kidneys from neonatal SHRs. If so, this may suggest that deregulation in the expression of WT-1 and its impact on nephrogenesis induction could be crucial in understanding the development and maintenance of hypertension.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0250-6) contains supplementary material, which is available to authorized users.

Early podocyte injury and elevated levels of urinary podocyte-derived extracellular vesicles in swine with metabolic syndrome: role of podocyte mitochondria

“…In the presence of ROS, cytochrome c peroxidase causes cardiolipin peroxidation and cristae degradation (4). Mitochondrial health is important for podocyte function, actin assembly (1), and protection from apoptosis (23) as well as for expression and trafficking of nephrin and WT1 (24,32). In our study, morphological analysis indicated structural damage to podocyte mitochondria in MetS, and cardiolipin colocalized well with WT1 staining, implicating mitochondrial injury in the podocyte pathology associated with MetS.…”

The protective role of vitamin D on the heart and the kidney

“…In this regard, we recently showed that changes in the expression pattern of the WT-1 transcription factor, a key mediator of nephrogenesis, could contribute to anatomical and functional kidney disorders linked to hypertension development. These changes could respond to VDR modulation ( Figure 1) [Mazzei et al 2016].…”

Consumption of oil macerated with garlic produces renovascular protective effects in adult apolipoprotein E-deficient mice

“…Membrane fractions were prepared as previously described. 8 The supernatant was separated and again centrifuged, this time at 19 500 rpm, and the protein concentration of the membrane fraction lysate was quantified by the Lowry assay using bovine serum albumin as a standard. A sample (40 μL) of the membrane fraction resuspended in lysis buffer was rapidly read using a spectrofluorometer (FluoroCount; AF10001, Cambers) to establish the basal value of each sample.…”

“…Likewise, renal expression of WT-1 during the organogenesis process is modulated by oxidative/ inflammatory alterations, and phenotypic alteration of WT-1, either in its expression and/or location, produces pathological states both at the vascular and renal levels. 8 In this regard, a suitable animal model for studying the pathophysiological processes associated with vascular dysfunction may be the spontaneously hypercholesterolemic apolipoprotein E knockout (ApoE-KO) mouse. A major function of ApoE is to transport lipids among various cells and tissues of the body, and as a constituent of high density lipoproteins (HDL) is involved in cholesterol homeostasis and lipid metabolism.…”

“…Likewise, renal expression of WT-1 during the organogenesis process is modulated by oxidative/inflammatory alterations, and phenotypic alteration of WT-1, either in its expression and/or location, produces pathological states both at the vascular and renal levels. 8…”