Mesenchymal-epithelial transition in the developing metanephric kidney: Gene expression study by differential display

Abstract

The developing metanephric kidney is a convenient model to study molecular events associated with epithelial cell differentiation. To determine the genes involved in the defining event of this process, namely, the conversion of metanephric mesenchyme to the epithelium of the nephron, we applied differential display (DD) techniques. Explants of rat metanephric mesenchymes were induced to condense ex vivo with fibroblast growth factor 2 (FGF2) or to form tubules with FGF2 and conditioned medium (CM) from a cell line (RUB1) of ureteric bud, the renal inductive tissue. Three time points (6, 24, and 72 h) were chosen to track the dynamics of gene expression during morphogenesis. Seventy-two up- or down-regulated mRNAs were identified, including 36 novel sequences and those of cell cycle regulatory proteins (TGF-beta2, Cyclin D1, p57Kip2), transcription factors (beta-catenin, Sox11, DP1), signaling proteins (SH3-domain binding protein, G-protein-coupled receptor, Ser-Thr protein kinase), cell adhesion molecules (syndecan-4, integrin-beta1), and also gene33, H19, SM20, IGFBP5, MAMA receptor, lectin, keratin, beta-tubulin, calreticulin, GRP78, ERp72, MnSoD, thioredoxin, and others. Some have previously been associated with kidney development and serve as good controls for expected changes, while most have not been linked with kidney epithelial cell differentiation. Using thin sections of embryonic kidney and labeled antisense RNA probes, we applied RNA hybridization to confirm the results of DD and related the expression of these genes to specific cell lineages of the developing kidney. These results provide a window into the events that mediate this critical differentiation process and suggest that a limited number of interrelated events direct the epithelial conversion of metanephric mesenchyme. genesis 27:22-31, 2000. Published 2000 Wiley-Liss, Inc.

Endoplasmic reticulum stress in the kidney

“…Currently, information is limited regarding whether and how ER stress and UPR are involved in the renal development, but a previous report showed that expression of GRP78 is induced in developing metanephric kidneys [67]. Further investigation will be required to clarify developmental significance of this observation and to identify roles of UPR in the kidney development.…”

Maternal nutrient restriction during pregnancy differentially alters the unfolded protein response in adipose and renal tissue of obese juvenile offspring

“…One potential mechanism of this apparent protective effect could be the in utero resetting of the threshold for UPR activation: that is, a greater degree of ER stress would need to occur prior to the activation of the deleterious effects of the UPR. This hypothesis is supported by the work of Plisov et al (44), who demonstrated that GRP78 was expressed in the developing metanephros, most notably within the cortical glomeruli, collecting ducts, and Figure 10. Proposed mechanism of increased PAT dysfunction observed in obese NR offspring.…”

Transcriptional Networks in Epithelial-Mesenchymal Transition

“…The transcription factors up-regulated in EMT are displayed in Table S3 together with their most frequent CREs . Underlined are four high CRE frequency transcription factors that were chosen for further study for their relevance to TGF-β-induced EMT ( Atf2 [48], [49], SP1 [50], [51], [52], Klf10 [53], [54], and Sox11 [55]). All four transcription factors are induced within 6 hours and remain up-regulated at 18 hours with two, Klf10 and Sox11 , being up-regulated throughout EMT.…”