Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells

Abstract

Nephron progenitor cells surround around the ureteric bud tips (UB) and inductively interact with the UB to originate nephrons, the basic units of renal function. This process is determined by the internal balance between self-renewal and consumption of the nephron progenitor cells, which is depending on the complicated regulation networks. It has been reported that Zeb1 regulates the proliferation of mesenchymal cells in mouse embryos. However, the role of Zeb1 in nephrons generation is not clear, especially in metanephric mesenchyme (MM). Here, we detected cell proliferation, apoptosis and migration in MM cells by EdU assay, flow cytometry assay and wound healing assay, respectively. Meanwhile, Western and RT-PCR were used to measure the expression level of Zeb1 and Six2 in MM cells and developing kidney. Besides, the dual-luciferase assay was conducted to study the molecular relationship between Zeb1 and Six2. We found that knock-down of Zeb1 decreased cell proliferation, migration and promoted cell apoptosis in MM cells and Zeb1 overexpression leaded to the opposite data. Western-blot and RT-PCR results showed that knock-down of Zeb1 decreased the expression of Six2 in MM cells and Zeb1 overexpression contributed to the opposite results. Similarly, Zeb1 promoted Six2 promoter reporter activity in luciferase assays. However, double knock-down of Zeb1 and Six2 did not enhance the apoptosis of MM cells compared with control cells. Nevertheless, double silence of Zeb1 and Six2 repressed cell proliferation. In addition, we also found that Zeb1 and Six2 had an identical pattern in distinct developing phases of embryonic kidney. These results indicated that there may exist a complicated regulation network between Six2 and Zeb1. Together, we demonstrate Zeb1 promotes proliferation and apoptosis and inhibits the migration of MM cells, in association with Six2.

Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy

“…A phenotypic clinical feature of FECD is the development of corneal guttae, which are abnormal collagenous excrescences of the corneal endothelial basement membrane (Descemet’s membrane). Recent studies have shown that Snail and ZEB1 can also reduce cell adhesion, increase cell migratory capacity [74–76], and promote apoptosis [77, 78]. These phenotypic features have also been observed during FECD pathogenesis [79–81].…”

Migratory potential of transplanted glial progenitors as critical factor for successful translation of glia replacement therapy: The gap between mice and men

“…EMT is a process that is prominent in embryonic development, but its aberrant induction is linked to invasiveness of epithelial cancer cells via promoting their migration, invasion, and dissemination (Zhang et al 2015). ZEB-1 increases EMT by suppression of CDH1 (encoding E cadherin, an epithelial marker) and microRNA 200 (Gu et al 2016). This leads to the activation of the TGF-β1 signaling pathway and elicits unregulated proliferation of cancer cells and their invasion (Gu et al 2016).…”

“…ZEB-1 increases EMT by suppression of CDH1 (encoding E cadherin, an epithelial marker) and microRNA 200 (Gu et al 2016). This leads to the activation of the TGF-β1 signaling pathway and elicits unregulated proliferation of cancer cells and their invasion (Gu et al 2016). In addition, ZEB-1 has been implicated in animal organ development, cartilage development, and regulation of MSC proliferation, as well as the establishment of a motile and drug-resistance tumor phenotype (Gu et al 2016).…”

“…This leads to the activation of the TGF-β1 signaling pathway and elicits unregulated proliferation of cancer cells and their invasion (Gu et al 2016). In addition, ZEB-1 has been implicated in animal organ development, cartilage development, and regulation of MSC proliferation, as well as the establishment of a motile and drug-resistance tumor phenotype (Gu et al 2016). However, there is little reference to the concrete role of ZEB-1 in the migration of stem cells.…”

Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney

“…When the signaling for the process of induction is successful, a few mesenchymal cells separate, aggregate, and perform a mesenchyme-to-epithelial transition (MET) to develop into a renal vesicle at the lateral aspect of the related CD ampulla [63]. For remaining and not induced mesenchymal cells, the transcription factor Zeb1 controls the balance between further proliferation, migration, and apoptosis [64]. Thus, repeated branching of a CD tubule, approximation of a CD ampulla tip to competent mesenchymal cells, and finally timely induction superimposes new nephrons beyond the capsule [42].…”