Related Experiment Video

Updated: Jun 1, 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

Hepatocyte growth factor attenuates transforming growth factor-β-angiotensin II crosstalk through inhibition of the

Kazuma Iekushi1, Yoshiaki Taniyama, Hiroshi Kusunoki

  • 1Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.

Hypertension (Dallas, Tex. : 1979)
|June 15, 2011
PubMed

Insights

Hepatocyte growth factor (HGF) protects kidneys by inhibiting the angiotensin II (Ang II)-transforming growth factor-beta1 (TGF-β1) pathway. HGF normalizes angiotensin type 1 receptor (AT(1)R) expression via the PTEN/Akt pathway, reducing kidney injury and fibrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Chronic kidney disease (CKD) progression involves angiotensin II (Ang II) and transforming growth factor-beta1 (TGF-β1).
  • Hepatocyte growth factor (HGF) exhibits protective effects against Ang II and TGF-β1 actions.
  • The interplay between Ang II, TGF-β1, and HGF in renal cells requires elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms by which HGF antagonizes the Ang II-TGF-β axis in renal cells.
  • To determine the role of the PTEN/Akt pathway in HGF's protective effects against TGF-β1-induced AT(1)R expression.
  • To validate the in vivo efficacy of HGF in mitigating Ang II-induced renal injury and fibrosis.

Main Methods:

  • In vitro studies using cultured human mesangial cells treated with TGF-β1 and Ang II.
  • Assessment of angiotensin type 1 receptor (AT(1)R) mRNA and phosphatase and tensin homolog (PTEN) expression and activity.
  • In vivo experiments using HGF transgenic (HGF-Tg) mice subjected to Ang II infusion.
  • Administration of a PTEN-specific inhibitor and a neutralizing antibody against HGF.

Main Results:

  • TGF-β1 increased AT(1)R mRNA and decreased PTEN expression/activity, dependent on the Akt/PI3K pathway.
  • Ang II enhanced TGF-β1 expression, indicating a positive feedback loop.
  • HGF attenuated TGF-β1-induced AT(1)R upregulation and PTEN downregulation, mediated by the PTEN/Akt pathway.
  • HGF-Tg mice showed reduced renal injury, fibrosis, AT(1)R expression, and increased PTEN levels after Ang II infusion.
  • HGF-neutralizing antibody abrogated the protective effects in HGF-Tg mice.

Conclusions:

  • HGF counteracts the pro-fibrotic Ang II-TGF-β1-AT(1)R axis in renal cells.
  • HGF's protective mechanism involves the upregulation of PTEN, thereby inhibiting the Akt/PI3K pathway and reducing AT(1)R expression.
  • HGF demonstrates significant renoprotective effects in vivo by mitigating Ang II-induced kidney injury and fibrosis.

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

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

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

Published on: August 3, 2018

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...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...