epidermal-growth-factor and Renal-Insufficiency

Chronic kidney disease (CKD) is the third-leading cause of premature mortality worldwide. It is characterized by rapid deterioration due to renal interstitial fibrosis (RIF) via excessive inflammatory infiltration. The aim of this study was to discover key immune-related genes (IRGs) to provide valuable insights and therapeutic targets for RIF in CKD.. We screened differentially expressed genes (DEGs) between RIF samples from CKD patients and healthy controls from a public database. Least absolute shrinkage and selection operator regression analysis and receiver operating characteristic curve analysis were applied to identify significant key biomarkers. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analyze the infiltration of immune cells between the RIF and control samples. The correlation between biomarkers and immune cell composition was assessed.. A total of 928 DEGs between CKD and control samples from six microarray datasets were found, 17 overlapping immune-correlated DEGs were identified by integration with the ImmPort database, and six IRGs were finally identified in the model: apolipoprotein H (APOH), epidermal growth factor (EGF), lactotransferrin (LTF), lysozyme (LYZ), phospholipid transfer protein (PLTP), and secretory leukocyte peptidase inhibitor (SLPI). Two additional datasets and. In summary, six IRGs were identified as key biomarkers for RIF, and exhibited a strong correlation with various T cells and with the NF-κB signaling pathway. All these IRGs and their signaling pathways may evolve as valuable therapeutic targets for RIF in CKD.

Topics: Biomarkers; Epidermal Growth Factor; Humans; NF-kappa B; Renal Insufficiency; Renal Insufficiency, Chronic; Signal Transduction

A delay in the diagnosis and treatment of iatrogenic obstructive ureteral injury is the most important prognostic factor for worse results in terms of lesion repair and renal function recovery. The role of the time of relief in determining the onset of renal failure and arterial hypertension in patients with obstructive ureteral injury was evaluated. In addition, we analyzed the prognostic value of the ratio of urinary epidermal growth factor-to-monocyte chemotactic peptide-1 in predicting long-term renal function deterioration.. A total of 76 patients with obstructive ureteral injury and treated with reconstructive procedures were prospectively enrolled in the study. The ratio of epidermal growth factor-to-monocyte chemotactic peptide-1 was evaluated 4 weeks after the relief of obstruction. After a median followup of 60.8 months, estimated creatinine clearance and (99m)technetium-mercaptoacetyltriglycine scan were evaluated.. Within 2 weeks of the obstructive ureteral injury 36 patients underwent surgery for relief of obstruction while in the remaining 40 patients the surgery was performed after more than 2 weeks. Significant differences between the 2 groups were observed regarding mean mercaptoacetyltriglycine clearance of the obstructed kidney (p <0.0001), estimated creatinine clearance (p <0.001) and ratio of epidermal growth factor-to-monocyte chemotactic peptide-1 (p <0.0001). There was a direct correlation between mercaptoacetyltriglycine clearance and epidermal growth factor-to-monocyte chemotactic peptide-1 (rs = 0.78, p <0.0001). Patients with a time of relief greater than 2 weeks had a higher incidence of postoperative hypertension. On logistic regression the time of relief was the only significant variable predicting renal function deterioration (OR 1.49, p = 0.01).. Patients who experience delayed relief of obstructive ureteral injury have decreased long-term renal function as suggested by the lower values of estimated creatinine clearance and mercaptoacetyltriglycine clearance, and are at risk for hypertension or exacerbation of preexisting hypertension.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Chemokine CCL2; Child; Child, Preschool; Creatine; Disease Progression; Epidermal Growth Factor; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Plastic Surgery Procedures; Prognosis; Prospective Studies; Renal Insufficiency; Time Factors; Ureter; Ureteral Obstruction; Urologic Surgical Procedures; Young Adult

It was reported that the parathyroid gland hyperplasia correlated with enhanced co-expression of TGF-alpha and its receptor EGFR at early stages of renal failure. This time, we investigated the time course for EGFR and its ligands, TGF-alpha, and EFG expression, and the influence of high-phosphorus (P) diet to EGFR and EGF expression, and the effect of EGFR-tyrosine kinase inhibitor (Gefitinib, [IRESSA; AstraZeneca]; TKI) in rat PTGs with established stage of renal failure. The levels of EGFR, EGF, TGF-alpha mRNA in rat PTGs were increased for the time periods. The serum intact PTH levels, and EGFR, EGFmRNA in rat PTGs were suppressed in normal-P diet group. Nuclei positive cells for PCNA in TKI group were suppressed. The levels of p21mRNA were increased in TKI group. These results suggested that the enhanced expression of EGFR, TGF-alpha and EGF participate in the cell proliferation of hyperplastic PTGs in established stage of renal failure.

Topics: Animals; Cell Proliferation; Disease Models, Animal; Epidermal Growth Factor; ErbB Receptors; Gefitinib; Hyperplasia; Intracellular Signaling Peptides and Proteins; Male; Parathyroid Glands; Parathyroid Hormone; Phosphorus, Dietary; Quinazolines; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Time Factors; Transforming Growth Factor alpha

Physiologically, OAT1 is located in the basolateral membrane of proximal tubular cells. During renal damage loss of polarity occurs in renal epithelial cells, leading to missorting of proteins or complete loss of polarity. Missorting or loss of polarity generally leads to disturbance of vectorial transport. In the present study, hOAT1 was expressed in human renal epithelial IHKE cells (IHKE-hOAT1) and in non polarized CHO cells (CHO-hOAT1). Because EGF and its receptor is described to play on important role in recovery from renal damage, we compared the regulation of hOAT1 by EGF in the (a) basolateral and (b) apical membrane of epithelial cells, and in (c) non polarized cells, resembling the above mentioned pathophysiological situations. Expression of hOAT1 was verified by determination of the kinetic parameters (using fluorescein as a substrate) and western blot (CHO-hOAT1) or RT-PCR (IHKE-hOAT1). To investigate the EGF effect on hOAT1, CHO-hOAT1 cells were additionally co-transfected with the human EGF receptor HER1. In agreement with previous publications, incubation of IHKE-hOAT1 cells with EGF increased fluorescein uptake via basolateral hOAT1. In opposite, EGF inhibited hOAT1 mediated fluorescein uptake across the apical membrane of IHKE-hOAT1 cells. Additionally EGF inhibited hOAT1 mediated fluorescein uptake into non polarized CHO-hOAT1-HER1 cells, too. In summary, we confirmed that EGF stimulates basolateral uptake of organic anions (a) in proximal tubular cells mediated by hOAT1. However, EGF inhibits hOAT1 located in the apical membrane (b) or in non polarized cells (c). Renal failure is associated with successive loss of epithelial polarity. Therefore, inverted regulation of hOAT1 falsely located in the apical membrane of proximal tubular cells may be part of a mechanism stabilizing organic anion secretion in pathophysiological situations.

Topics: Animals; Cell Line; Cell Membrane; Cell Polarity; Cricetinae; Epidermal Growth Factor; Epithelial Cells; ErbB Receptors; Gene Expression Regulation; Humans; Kidney Tubules, Proximal; Organic Anion Transport Protein 1; Recombinant Proteins; Renal Insufficiency; Transfection

We describe an ELISA technique for quantification of fetal antigen 1 (FA1), a glycoprotein belonging to the EGF-superfamily. The ELISA is based on immunospecifically purified polyclonal antibodies and has a dynamic range of 0.7-5.3 ng/ml, intra- and inter-assay C.V.s of less than 3.2% and an average recovery of 105% in serum and 98% in urine. Comparison of FA1 in amniotic fluid, serum and urine revealed parallel titration curves, identical elution volumes following size chromatography, immunological identity and similar profiles when analysed by MALDI-MS. The reference interval for serum FA1 was 12.3-46.6 ng/ml and the levels were 10 times higher in patients with renal failure. FA1 showed no diurnal variation, no variation during the menstrual cycle and was not influenced by the acute phase reaction. In humans (n = 10) the renal clearance of FA1 was 11 ml/min and an identical high renal clearance was found in rats when expressed per 100 g body weight. In rats the initial increase in serum FA1 was 10 ng/ml/h following bilateral nephrectomy, explaining the increased serum concentrations of FA1 observed in patients with renal failure.

Topics: Acute-Phase Reaction; Adult; Animals; beta 2-Microglobulin; Chromatography, Affinity; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Glycoproteins; Humans; Kidney; Lymph; Male; Middle Aged; Nephrectomy; Rats; Rats, Inbred Lew; Reference Values; Renal Insufficiency; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Contents of epidermal growth factor (EGF) in urine, plasma and tissues in urological diseases were estimated by enzyme immunoassay using beads bound to the anti-EGF antibody, and the clinical significance of the presence of EGF in the disease state was examined. There was no difference in EGF level between healthy male and female subjects (n = 22), and the level showed a tendency to decrease with age (p less than 0.05). The subjects were 19 cases of prostatic cancer, 7 of renal cancer, and 12 of urinary bladder cancer. The difference in EGF level between the healthy subjects and patients was not significant, and the levels were shown to be lower in 8 cases of renal insufficiency (including patients on hemodialysis:HD)(p less than 0.01). Plasma EGF levels in the 30 healthy subjects revealed no significant differences related to sex or age. Plasma EGF levels were lower in 42 cases of renal insufficiency (before and after HD), and in 7 cases of renal cancer (p less than 0.01); they ware significantly lower in 15 cases of prostatic cancer (p less than 0.05). In tissues including tumor sites, EGF levels were higher particularly in the prostatic gland tissue (hypertrophy and cancer regions). Thus, urinary and plasma EGF levels in urological diseases may be useful parameters of renal function, but its relationship with malignant diseases is still unknown. The EGF level should be explored in relation with the EGF receptor.

Topics: Adult; Age Factors; Aged; Epidermal Growth Factor; Female; Humans; Kidney; Kidney Neoplasms; Male; Middle Aged; Prostate; Prostatic Neoplasms; Reference Values; Renal Insufficiency; Urologic Diseases