Related Experiment Video

Updated: May 9, 2026

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
13:51

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

The small GTPase N-Ras regulates extracellular matrix synthesis, proliferation and migration in fibroblasts

Isabel Fuentes-Calvo1, Piero Crespo2, Eugenio Santos3

  • 1Unidad de Fisiopatología Renal y Cardiovascular, Instituto "Reina Sofía" de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.

Biochimica Et Biophysica Acta
|July 23, 2013
PubMed

Insights

N-Ras deficiency in fibroblasts increases basal collagen synthesis while reducing proliferation and migration. N-Ras modulates transforming growth factor-β1 (TGF-β1) signaling, impacting extracellular matrix production in renal fibrosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Renal Pathophysiology

Background:

  • Ras GTPases are crucial regulators of cellular functions and oncogenes.
  • Transforming growth factor-β1 (TGF-β1) signaling pathways are closely linked with Ras GTPases.
  • Different Ras isoforms (H-Ras, N-Ras, K-Ras) modulate distinct cellular pathways.

Purpose of the Study:

  • To investigate the role of N-Ras in renal fibrosis development.
  • To assess N-Ras's individual contribution to extracellular matrix (ECM) synthesis, proliferation, and migration.
  • To analyze N-Ras function in both basal and TGF-β1-mediated cellular processes using N-Ras deficient fibroblasts.

Main Methods:

  • Utilized immortalized N-Ras deficient fibroblasts (N-ras(-/-)) and their normal counterparts.
  • Assessed basal and TGF-β1-stimulated phosphatidylinositol-3-kinase (PI3K)/Akt and MEK/Erk signaling pathways.
  • Quantified collagen synthesis, fibroblast proliferation, and migration rates.

Main Results:

  • N-Ras deficient fibroblasts showed higher basal PI3K/Akt and MEK/Erk activity, increased collagen synthesis, and decreased proliferation and migration.
  • TGF-β1-induced proliferation and migration were independent of N-Ras but reliant on PI3K/Akt activation.
  • TGF-β1-induced expression of fibronectin and collagen type I was regulated by N-Ras through Erk-independent pathways.

Conclusions:

  • N-Ras may contribute to renal fibrosis by down-regulating ECM synthesis and up-regulating proliferation and migration via Akt modulation.
  • N-Ras plays a significant role in regulating TGF-β1-induced collagen I and fibronectin expression through Erk-independent mechanisms.
Keywords:
ECMMEK-Erk1/2MEK/ERK 1/2PI3K-AktPI3K/AktRas proteinsRenal fibrosisTGF-β1Transforming growth factor-β1extracellular matrixmitogen activated protein kinase 2-extracellular signal regulated kinase 1/2phosphatidyl inositol 3 kinase-protein kinase Btransforming growth factor-β1

More Related Videos

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates11:28

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates

Published on: March 31, 2012

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...