Related Experiment Video

Updated: Mar 14, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

11.9K

Dact1, a Wnt-Pathway Inhibitor, Mediates Human Mesangial Cell TGF-β1-Induced Apoptosis

Daniele Pereira Jardim1,2, Paula Cristina Eiras Poço1, Alexandre Holthausen Campos1

  • 1Centro de Pesquisa Experimental, Instituto Israelita de Ensino e Pesquisa, Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.

Journal of Cellular Physiology
|October 8, 2016
PubMed

Insights

Transforming growth factor-β1 (TGF-β1) induces kidney cell death by upregulating the Dact1 gene. This novel pathway inhibits the pro-survival Wnt pathway, contributing to chronic kidney disease progression.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Chronic kidney disease (CKD) is a global health issue.
  • Mesangial cell (MC) loss is an early feature of CKD pathogenesis.
  • Transforming growth factor-β1 (TGF-β1) induces kidney damage and MC apoptosis, but the mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism of TGF-β1-induced MC apoptosis.
  • To identify novel regulatory pathways involved in CKD pathogenesis.

Main Methods:

  • Investigated the role of disheveled-binding antagonist of β-catenin 1 (Dact1) in TGF-β1-induced MC apoptosis.
  • Examined Dact1 mRNA and protein levels in a rat model of CKD (5/6 nephrectomy).
  • Assessed the effect of Dact1 and TGF-β1 on Wnt pathway transcriptional activation.

Main Results:

  • TGF-β1 upregulates Dact1 gene expression, leading to MC apoptosis.
  • Dact1 and TGF-β1 inhibit the pro-survival Wnt pathway, mediating MC death.
  • Increased Dact1 levels in kidney remnants of nephrectomized rats correlate with TGF-β1 expression.

Conclusions:

  • Dact1 is a novel regulator of MC survival.
  • The Dact1/TGF-β1 pathway contributes to CKD progression by inducing MC apoptosis and inhibiting the Wnt pathway.

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

1.0K
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

14.7K

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - 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...
10.8K
Canonical Wnt Signaling Pathway02:54

Canonical 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...
10.9K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.1K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.2K