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FGF-10 is decreased in bronchopulmonary dysplasia and suppressed by Toll-like receptor activation

John T Benjamin1, Rebekah J Smith, Brian A Halloran

  • 1Departments of Pediatrics, Children's Hospital of Alabama, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|October 31, 2006
PubMed

Insights

Fibroblast growth factor-10 (FGF-10) is crucial for saccular lung development. Its reduction, triggered by innate immune activation via Toll-like receptors (TLRs), contributes to bronchopulmonary dysplasia in preterm infants.

Area of Science:

  • Pulmonary Medicine
  • Developmental Biology
  • Immunology

Background:

  • Bronchopulmonary dysplasia (BPD) is a common complication in extremely preterm infants, characterized by abnormal saccular-stage lung development.
  • Fibroblast growth factor-10 (FGF-10) plays a vital role in normal lung development, but its role in BPD pathogenesis is unclear.
  • The link between inflammatory stimuli, such as bacterial exposure, and abnormal lung development in BPD remains mechanistically undefined.

Purpose of the Study:

  • To investigate the role of FGF-10 in saccular lung development.
  • To determine if inflammatory pathways, specifically Toll-like receptor (TLR) activation, impact FGF-10 expression during lung development.
  • To explore the potential connection between FGF-10 dysregulation and the characteristic myofibroblast abnormalities observed in BPD.

Main Methods:

  • Utilized an experimental mouse model to study saccular lung development.
  • Examined FGF-10 expression in lung tissue from infants with and without BPD.
  • Investigated the effects of activating Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) on FGF-10 expression and lung morphogenesis.
  • Assessed the localization of myofibroblasts around saccular airways.

Main Results:

  • FGF-10 is essential for normal saccular lung development and is reduced in infants with BPD.
  • Activation of TLR2 or TLR4 in a mouse model significantly inhibited FGF-10 expression.
  • TLR-mediated inhibition of FGF-10 led to abnormal saccular airway morphogenesis and disrupted myofibroblast positioning.
  • The observed myofibroblast mislocalization mimicked that seen in human BPD cases.

Conclusions:

  • FGF-10 is a critical mediator of saccular lung development.
  • Innate immune activation through TLRs can suppress FGF-10 expression, leading to impaired lung development.
  • Reduced FGF-10 expression represents a potential molecular link between innate immune responses and the pathogenesis of bronchopulmonary dysplasia.

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