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The distribution of endothelin-converting-enzyme-1 (ECE-1) messenger ribonucleic acid (mRNA) and its protein in the human kidney was assessed by implementing immunochemistry and hybridization at the site. The results revealed that ECE-1 is dispersed throughout the human kidney in vascular endothelial and tubular epithelial cells. The comparison made between the manner of distribution of ECE-1 and anti-von Willebrand factor had established the endothelial mechanism of the cells studied.

Investigates the distribution of the endothelin-converting enzyme-1 (ECE-1) messenger ribonucleic acid (mRNA) and protein in human kidney. Detection of ECE-1 immunoreactivity in the cortex and medualla of the kidney; Distribution patterns of ECE-1 mRNA; Optical density of ECE-1 mRNA autoradiographic signals.

Polyploidization of tubular cells (TC) is triggered by acute kidney injury (AKI) to allow survival in the early phase after AKI, but in the long run promotes fibrosis and AKI-chronic kidney disease (CKD) transition. The molecular mechanism governing the link between polyploid TC and kidney fibrosis remains to be clarified. In this study, we demonstrate that immediately after AKI, expression of cell cycle markers mostly identifies a population of DNA-damaged polyploid TC. Using transgenic mouse models and single-cell RNA sequencing we show that, unlike diploid TC, polyploid TC accumulate DNA damage and survive, eventually resting in the G1 phase of the cell cycle. In vivo and in vitro single-cell RNA sequencing along with sorting of polyploid TC shows that these cells acquire a profibrotic phenotype culminating in transforming growth factor (TGF)-β1 expression and that TGF-β1 directly promotes polyploidization. This demonstrates that TC polyploidization is a self-sustained mechanism. Interactome analysis by single-cell RNA sequencing revealed that TGF-β1 signaling fosters a reciprocal activation loop among polyploid TC, macrophages, and fibroblasts to sustain kidney fibrosis and promote CKD progression. Collectively, this study contributes to the ongoing revision of the paradigm of kidney tubule response to AKI, supporting the existence of a tubulointerstitial cross talk mediated by TGF-β1 signaling produced by polyploid TC following DNA damage. NEW & NOTEWORTHY Polyploidization in tubular epithelial cells has been neglected until recently. Here, we showed that polyploidization is a self-sustained mechanism that plays an important role during chronic kidney disease development, proving the existence of a cross talk between infiltrating cells and polyploid tubular cells. This study contributes to the ongoing revision of kidney adaptation to injury, posing polyploid tubular cells at the center of the process.

Regulatory T cells (T(reg)) migrate into allografts and induce tolerance of the graft. Immunosuppressive T(reg) are found among CD4+CD25++ T cells and specifically express the forkhead/winged transcription factor FOXP3. We hypothesized that activated T cells and T(reg) might modulate the ongoing inflammation of the cardiac allograft (CA) and that the chronic inflammatory environment might influence the balance between these distinct cell types. We therefore quantified levels of activated T cells and CD4+CD25++ T(reg) in the cardiac and systemic circulation in heart transplant recipients. To determine the influence of the allograft passage on these cells, transcardiac gradients were evaluated in CA recipients (n = 22) compared with controls (n = 18). Systemic levels of circulating T(reg) were significantly lower in CA recipients (8.9 +/- 1.3 microl) compared with controls (15.8 +/- 1.6 microl; P = 0.002). Similarly, the proportion of T(reg) related to the total leukocyte number was significantly lower in CA recipients (P < 0.01). In contrast, systemic levels of circulating activated CD4+ T cells and of circulating plasmacytoid dendritic cells were similar in both groups. In transplant patients, numbers of T(reg) significantly decreased during transcardiac passage (3.0 +/- 0.3 to 2.4 +/- 0.3% of CD4+ T cells, P < 0.01), and FOXP3+ T cells invaded into the allograft. In contrast, numbers of activated CD4+ T cells increased during passage through the allograft, even in the presence of effective immunosuppression. In conclusion, numbers of circulating immunosuppressive T(reg) are reduced in transplant recipients. Recruitment of T(reg) into the cardiac allograft during transcoronary passage may induce graft tolerance during subclinical inflammation potentially influencing allograft vasculopathy.