Transcript- and Protein-Level Preservation and Spatial Reorganization of EMT and Vascular–Mesenchymal Gene Programs (SNAI1, TGFB1, PECAM1, VIM) in Human Fetal Kidneys with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)

Abstract

Background/Objectives: Congenital anomalies of the kidney and urinary tract (CAKUT) are a leading cause of pediatric kidney disease. Epithelial–mesenchymal transition (EMT), governed by SNAI1 and TGF-β, and a vascular–mesenchymal program marked by PECAM1 and VIM are central to nephrogenesis, but whether these programs are transcriptionally activated in human CAKUT is unknown. We assessed their expression and spatial organization in human fetal kidneys. Methods: We reanalyzed public transcriptomic datasets for six transcripts (SNAI1, TGFB1–3, PECAM1, VIM) and performed quantitative double immunofluorescence for four gene products (SNAIL, TGF-β1, CD31, vimentin) on formalin-fixed human fetal kidneys (20 controls, 19 CAKUT), with colocalization quantified by Pearson’s coefficient. Results: No statistically significant difference in transcript or protein abundance was detected between control and CAKUT kidneys, in either the cortex or the medulla, and abundance did not change across developmental phases. In contrast, spatial colocalization of SNAIL–TGF-β and of CD31–vimentin was increased in CAKUT kidneys. Conclusions: These findings may suggest that, in human fetal CAKUT, EMT and vascular–mesenchymal programs are not quantitatively upregulated but instead show altered spatial organization of otherwise unchanged gene products. As colocalization reflects spatial proximity rather than molecular interaction, these observations are correlative and warrant functional validation.