RESUMEN
Regenerative therapy is considered a novel option for treating various diseases, whereas a developing embryo is a prime source of molecules that help repair diseased tissue and organs. Organoid culture studies also confirmed the inherent biological functions of several embryonic factors. However, the in vivo safety and efficacy of embryonic protein fraction (EPF) were not validated. In this study, we investigated the effectiveness of EPF on healthy adult rats. We obtained embryos from SD female rats of E14, E16, and E19 embryonic days and collected protein lysate. This lysate was administered intravenously into adult Sprague-Dawley rats on sequential days. We collected blood and performed hematological and biochemical parameters of rats that received EPF. C-reactive protein levels, interleukin-6, blood glucose levels, serum creatinine, blood urea, total leucocyte counts, and % of neutrophils and lymphocytes were comparable between rats receiving EPF and saline. Histological examination of rats' tissues administered with EPF is devoid of abnormalities. Our study revealed that intravenous administration of EPF to healthy adult rats showed that EPF is non-immunogenic, non-inflammatory, non-tumorigenic and safe for in vivo applications. Our analysis suggests that EPF or its components could be recommended for validating its therapeutic abilities in organ regenerative therapy.
RESUMEN
BACKGROUND: The prevalence of obesity is increasing worldwide at an alarming rate. In addition to the increased incidence of cardiovascular and metabolic diseases, obesity is the most potent risk factor for developing chronic kidney disease (CKD). Although systemic events such as hemodynamic factors, metabolic effects, and lipotoxicity were implicated in the pathophysiology of obesity-related glomerulopathy (ORG) and kidney dysfunction, the precise mechanisms underlying the association between obesity and CKD remain unexplored. METHODS: In this study, we employed spontaneous WNIN/Ob rats to investigate the molecular events that promote ORG. Further, we fed a high-fat diet to mice and analyzed the incidence of ORG. Kidney functional parameters, micro-anatomical manifestations, and podocyte morphology were investigated in both experimental animal models. Gene expression analysis in the rodents was compared with human subjects by data mining using Nephroseq and Kidney Precision Medicine Project database. RESULTS: WNIN/Ob rats were presented with proteinuria and several glomerular deformities, such as adaptive glomerulosclerosis, decreased expression of podocyte-specific markers, and effacement of podocyte foot process. Similarly, high-fat-fed mice also showed glomerular injury and proteinuria. Both experimental animal models showed increased expression of podocyte-specific transcription factor WT1. The altered expression of putative targets of WT1 such as E-cadherin, podocin (reduced), and α-SMA (increased) suggests elevated expression of WT1 in podocytes elicits mesenchymal phenotype. Curated data from CKD patients revealed increased expression of WT1 in the podocytes and its precursors, parietal epithelial cells. CONCLUSION: WT1 is crucial during nephron development and has minimal expression in adult podocytes. Our study discovered elevated expression of WT1 in podocytes in obesity settings. Our analysis suggests a novel function for WT1 in the pathogenesis of ORG; however, the precise mechanism of WT1 induction and its involvement in podocyte pathobiology needs further investigation.