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DDR1 role in fibrosis and its pharmacological targeting

Solange Moll1, Alexis Desmoulière2, Marcus J Moeller3

  • 1Department of Pathology, University Hospital of Geneva, Switzerland; Department of Pathology, Lausanne University Hospital, Switzerland.

Biochimica Et Biophysica Acta. Molecular Cell Research
|April 8, 2019
PubMed

Insights

Discoidin domain receptor 1 (DDR1), a collagen-activated kinase, shows promise as an anti-fibrotic target. Research explores its role in fibrotic diseases and potential therapeutic strategies.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen.
  • DDR1 is expressed in epithelial cells across multiple organs, including skin, kidney, liver, and lung.
  • Its precise biological functions and downstream pathways remain largely unknown, but it may influence fibroblast activation.

Purpose of the Study:

  • To review the evidence supporting DDR1 as an anti-fibrotic target.
  • To clarify DDR1's tissue distribution in both healthy and diseased states.
  • To explore DDR1's protective mechanisms and current pharmacological development efforts.

Main Methods:

  • Literature review of existing studies on DDR1.
  • Analysis of DDR1 expression patterns in various tissues and conditions.
  • Synthesis of evidence regarding DDR1's role in fibrosis and potential therapeutic interventions.

Main Results:

  • Increased DDR1 expression is observed in fibrotic conditions like hypertrophic scars, idiopathic pulmonary fibrosis, liver cirrhosis, and renal fibrosis.
  • DDR1 may mediate stromal-epithelial interactions, potentially regulating quiescent fibroblast activation.
  • Evidence suggests DDR1 has a protective role in fibrotic processes.

Conclusions:

  • DDR1 is a significant anti-fibrotic target with a protective mode of action.
  • Understanding DDR1's tissue distribution and biological pathways is crucial for therapeutic development.
  • Pharmacological strategies targeting DDR1 are under investigation for treating fibrotic diseases.
Keywords:
DDR1FibrosisKidneyLungSkinTyrosine kinase

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