DDR1 Modulates Cytoskeletal Remodeling and Podosome Formation in Renal Fibroblasts

Area of Science:

• Cell Biology
• Renal Fibrosis
• Extracellular Matrix Dynamics

Background:

• Discoidin domain receptor 1 (DDR1) is implicated in fibrotic progression in organs like the kidney.
• The precise role of DDR1 in renal fibroblast cytoskeletal organization and extracellular matrix remodeling is not fully understood.

Purpose of the Study:

• To investigate the regulation of DDR1 expression by profibrotic stimuli and matrix stiffness.
• To determine how DDR1 influences cytoskeletal organization and collagen remodeling in renal fibroblasts.

Main Methods:

• Single-cell RNA sequencing in a murine unilateral ureteral obstruction (UUO) model.
• In vitro studies using transforming growth factor-β1 (TGF-β1) stimulation and DDR1 depletion.
• Atomic force microscopy to assess collagen matrix stiffness.

Main Results:

• DDR1 expression was enriched in activated transitional fibroblasts during kidney injury.
• TGF-β1 increased DDR1 expression; DDR1 depletion suppressed stress fibers and promoted podosome formation.
• DDR1 deficiency led to impaired focal adhesions, enhanced collagen degradation, reduced gel contraction, and decreased matrix stiffness.

Conclusions:

• DDR1 modulates cytoskeletal remodeling in renal fibroblasts.
• DDR1 influences the balance between matrix degradation and contractile remodeling programs.
• A bidirectional relationship exists between DDR1 expression and extracellular matrix mechanics in the kidney.