Related Experiment Video
Updated: May 9, 2026
06:54
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TGFβ and CCN2/CTGF mediate actin related gene expression by differential E2F1/CREB activation
Noel Faherty1, Helen O'Donovan, David Kavanagh
1UCD School of Biomolecular and Biomedical Sciences, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
BMC Genomics
|August 2, 2013
Summary
Transforming growth factor beta (TGFβ) and connective tissue growth factor (CCN2) alter gene expression in diabetic nephropathy. This impacts actin dynamics and cell growth, potentially causing kidney dysfunction.
Area of Science:
- Cellular and Molecular Biology
- Renal Pathophysiology
- Gene Expression Analysis
Background:
- Connective tissue growth factor (CCN2/CTGF) is a key mediator in TGFβ-driven diabetic nephropathy.
- Previous studies identified CCN2 and TGFβ interactions that affect cell differentiation and migration.
- This study investigates the gene expression profile and transcriptional basis for these cellular changes.
Purpose of the Study:
- To define the gene expression profile associated with CCN2 and TGFβ interaction in diabetic nephropathy.
- To identify the transcriptional regulators responsible for altered actin dynamics and cell hypertrophy.
- To explore the role of Cdc42 in this signaling pathway.
Main Methods:
- Co-inertia analysis to identify key transcription factors.
- Experimental verification of identified transcription factors (E2F1, CREB).
- Analysis of actin and cytoskeletal gene expression in patient samples.
Main Results:
- E2F1 and CREB were identified as key regulators of actin dynamics and cell hypertrophy.
- Actin-related genes with E2F1 and CREB binding sites showed differential expression.
- Cdc42 activation was observed, and its interacting genes were dysregulated in diabetic nephropathy.
- These molecular changes were recapitulated in patient-derived renal disease tissues.
Conclusions:
- TGFβ and CCN2 modulate CREB and E2F1 activity, impacting actin cytoskeletal and cell growth genes.
- These alterations contribute to cell dysfunction in diabetic kidney disease.
- The cytoskeletal regulator Cdc42 may be involved in this pathological signaling cascade.
Related Concept Videos
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
02:54Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
01:30General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...