Related Experiment Video

Updated: Aug 17, 2026

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
08:09

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice

Published on: March 24, 2017

Antifibrotic therapy in scleroderma: extracellular or intracellular targeting of activated fibroblasts?

John Varga1

  • 1Section of Rheumatology (M/C 733), University of Illinois College of Medicine, Room 1158, Molecular Biology Research Building, 900 South Ashland Avenue, Chicago, IL 60607, USA. jvarga@uic.edu

Current Rheumatology Reports
|March 16, 2004
PubMed

Insights

Targeting transforming growth factor-beta (TGF-beta) shows promise for treating scleroderma fibrosis. However, potential adverse effects and fibroblast resistance necessitate careful consideration for anti-TGF-beta therapies.

Area of Science:

  • Immunology
  • Rheumatology
  • Fibrosis Research

Background:

  • Anticytokine therapies have transformed chronic inflammatory disease treatment.
  • Transforming growth factor-beta (TGF-beta) is a key factor in fibrosis pathogenesis, making it a target for scleroderma.
  • Concerns exist regarding potential overlapping cytokine roles and TGF-beta's homeostatic functions.

Purpose of the Study:

  • To review experimental evidence regarding concerns with anti-TGF-beta interventions for scleroderma.
  • To explore potential adverse consequences of blocking TGF-beta.
  • To indicate rational approaches to overcome challenges in anti-TGF-beta therapy.

Main Methods:

  • Literature review of experimental evidence on TGF-beta in fibrosis.
  • Analysis of scleroderma fibroblast behavior in response to TGF-beta signaling.
  • Evaluation of potential risks and benefits of anti-TGF-beta strategies.

Main Results:

  • Blocking TGF-beta may have significant adverse effects due to its homeostatic roles.
  • Scleroderma fibroblasts might be autonomously activated and unresponsive to TGF-beta blockade.
  • Overlapping functions of multiple cytokines in fibrosis pathogenesis present a challenge.

Conclusions:

  • A cautious approach is warranted for anti-TGF-beta therapies in scleroderma.
  • Strategies to overcome fibroblast resistance and mitigate adverse effects are crucial.
  • Further research is needed to refine anti-TGF-beta interventions for fibrotic diseases.

More Related Videos

Second Harmonic Generation Signals in Rabbit Sclera As a Tool for Evaluation of Therapeutic Tissue Cross-linking (TXL) for Myopia12:25

Second Harmonic Generation Signals in Rabbit Sclera As a Tool for Evaluation of Therapeutic Tissue Cross-linking (TXL) for Myopia

Published on: January 6, 2018

Ex Vivo Corneal Organ Culture Model for Wound Healing Studies06:46

Ex Vivo Corneal Organ Culture Model for Wound Healing Studies

Published on: February 15, 2019

Related Concept Videos

Introduction to Fibroblasts01:09

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
Fibril-associated Collagen01:11

Fibril-associated Collagen

Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
Fibronectins Connect Cells with ECM01:25

Fibronectins Connect Cells with ECM

Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
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...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...