Related Experiment Video

Updated: Jun 1, 2026

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
10:15

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection

Published on: November 10, 2021

Discoidin domain receptor 1 is a major mediator of inflammation and fibrosis in obstructive nephropathy

Dominique Guerrot1, Monique Kerroch, Sandrine Placier

  • 1INSERM UMR S 702, Hôpital Tenon, Paris, France; UPMC Paris 6 University, Paris, France.

The American Journal of Pathology
|June 7, 2011
PubMed

Insights

Discoidin domain receptor 1 (DDR1) promotes renal inflammation and fibrosis. Inhibiting DDR1 may offer a new therapeutic strategy for kidney diseases by reducing inflammatory cell infiltration and extracellular matrix accumulation.

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Tubulointerstitial inflammation and extracellular matrix remodeling are key drivers of renal fibrosis.
  • Discoidin domain receptor 1 (DDR1), a collagen-binding tyrosine kinase, influences cell behavior and matrix remodeling.
  • Previous studies show DDR1 deficiency protects against hypertension-related renal fibrosis.

Purpose of the Study:

  • To investigate the role of DDR1 in renal inflammation and fibrosis following unilateral ureteral obstruction (UUO).
  • To elucidate DDR1's specific contribution to tubulointerstitial injury.

Main Methods:

  • Unilateral ureteral obstruction (UUO) model in DDR1 knockout (DDR1(-/-)) and wild-type mice.
  • Kidney histopathology, quantitative PCR, and intravital microscopy were employed.
  • Macrophage polarization and migration assays were performed.

Main Results:

  • DDR1 expression significantly increased in obstructed kidneys.
  • DDR1(-/-) mice showed reduced collagen deposition, TGF-β, and pro-inflammatory cytokine levels.
  • Macrophage migration was impaired in DDR1(-/-) mice, despite normal M1/M2 polarization.

Conclusions:

  • DDR1 exacerbates renal inflammation and fibrosis in a UUO model.
  • DDR1 signaling contributes to macrophage recruitment and activation in the kidney.
  • Targeting DDR1 presents a potential therapeutic avenue for progressive renal diseases.

Related Concept Videos

Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
Inflammatory Bowel Disease II: Ulcerative Colitis01:20

Inflammatory Bowel Disease II: Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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),...