Related Experiment Video

Updated: Jun 21, 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

Transforming growth factor-beta2 upregulates sphingosine kinase-1 activity, which in turn attenuates the fibrotic

Shuyu Ren1, Andrea Babelova, Kristin Moreth

  • 1Institute of Pharmacology, University of Bern, Switzerland.

Kidney International
|August 7, 2009
PubMed

Insights

Sphingosine kinase-1 (SK-1) protects against kidney fibrosis by reducing connective tissue growth factor (CTGF) expression. Loss or inhibition of SK-1 activity worsens renal disease, highlighting its protective role.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Transforming growth factor-beta2 (TGF-beta2) promotes renal fibrosis by upregulating connective tissue growth factor (CTGF).
  • Sphingosine kinase-1 (SK-1) activity is also modulated by TGF-beta, suggesting a potential role in fibrotic processes.

Purpose of the Study:

  • To investigate the role of SK-1 in TGF-beta2-induced CTGF expression and renal fibrosis.
  • To determine the therapeutic potential of SK-1 in kidney disease.

Main Methods:

  • Utilized an immortalized human podocyte cell line and a mouse model of streptozotocin-induced diabetic nephropathy.
  • Assessed SK-1 and CTGF expression via mRNA and protein analysis.
  • Employed small interfering RNA (siRNA) for SK-1 depletion and pharmacological inhibitors.
  • Examined SK-1 deficient mice and wild-type controls.

Main Results:

  • TGF-beta2 activated SK-1 promoter, increasing SK-1 mRNA and protein in podocytes.
  • SK-1 depletion or inhibition accelerated CTGF expression.
  • SK-1 overexpression reduced CTGF induction, mediated by sphingosine-1-phosphate.
  • SK-1 and CTGF were upregulated in podocytes of patients with diabetic nephropathy and in a mouse model.
  • SK-1 deficient mice exhibited exacerbated kidney disease, with increased albuminuria and CTGF expression.

Conclusions:

  • SK-1 plays a protective role in the fibrotic process of renal disease.
  • Loss or inhibition of SK-1 activity aggravates fibrotic kidney disease, suggesting SK-1 as a potential therapeutic target.

More Related Videos

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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
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...