Related Experiment Video

Updated: May 15, 2026

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

Angiopoietin-like protein 2, a chronic inflammatory mediator, is a new target induced by TGF-β1 through a

Hee Jae Lee1, Jun Hwan Kim, Joon-Hyung Kim

  • 1Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

Biochemical and Biophysical Research Communications
|December 25, 2012
PubMed

Insights

Transforming growth factor-beta 1 (TGF-β1) upregulates Angiopoietin-like protein 2 (Angptl2) via a Smad3-dependent pathway. This Smad3 protein binds to the Angptl2 promoter, offering molecular insights into obesity-related inflammation.

Area of Science:

  • Molecular biology
  • Immunology
  • Endocrinology

Background:

  • Obesity elevates Angiopoietin-like protein 2 (Angptl2), an inflammatory mediator from adipocytes.
  • Transforming growth factor-beta 1 (TGF-β1) is increased in obesity but inhibits adipocyte differentiation.
  • The interplay between TGF-β1 and Angptl2 in obesity remains incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanism by which TGF-β1 influences Angptl2 expression.
  • To investigate the role of the Smad3 signaling pathway in TGF-β1-induced Angptl2 gene expression.

Main Methods:

  • Utilized RAW264.7 macrophage cells, primary peritoneal macrophages, and differentiated 3T3-L1 adipocytes.
  • Employed small interfering RNA (siRNA) to knockdown Smad3 expression.
  • Analyzed Angptl2 gene expression and Smad3 binding to the Angptl2 promoter.

Main Results:

  • TGF-β1 significantly induced Angptl2 gene expression in all tested cell types.
  • This induction was dependent on the Smad3 protein, which bound to the Smad Binding Element (SBE) on the Angptl2 promoter.
  • Smad3 knockdown reduced TGF-β1-induced Angptl2 expression in macrophages.

Conclusions:

  • TGF-β1 upregulates Angptl2 expression through a Smad3-dependent transcriptional mechanism.
  • These findings provide a molecular basis for the elevated Angptl2 and TGF-β1 levels observed in obesity.
  • The Smad3 pathway is a key regulator linking TGF-β1 signaling to Angptl2 in the context of obesity-related inflammation.

More Related Videos

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing07:05

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing

Published on: February 26, 2021

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 are of three kinds RI, RII, and RIII. The RI...
Regulation of Angiogenesis and Blood Supply01:24

Regulation 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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Chronic Inflammation: Introduction01:12

Chronic Inflammation: Introduction

Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...