Basic fibroblast growth factor decreases elastin production by neonatal rat lung fibroblasts

Area of Science:

• Pulmonary development and cell biology
• Extracellular matrix synthesis regulation

Background:

• Elastin synthesis by interstitial fibroblasts is crucial during lung development and alveolar septal elongation.
• The regulation of fibroblast elastin production is not fully understood, though growth factors play a role.
• A decrease in endothelial cell mitosis during alveolarization suggests a potential role for basic fibroblast growth factor (bFGF).

Purpose of the Study:

• To investigate the effect of basic fibroblast growth factor (bFGF) on elastin production by lung interstitial fibroblasts (LF).
• To determine if bFGF influences elastin gene transcription and endogenous elastin synthesis.

Main Methods:

• Quantification of elastin precursor tropoelastin (TE) synthesis using radiolabeled valine incorporation in cultured LF.
• Analysis of elastin mRNA levels via Northern blot.
• Assessment of elastin promoter activity using a transient transfection assay with an elastin promoter/CAT gene construct.
• Investigation of endogenous bFGF effects using an anti-bFGF antibody.

Main Results:

• Exogenous bFGF significantly decreased the synthesis of newly synthesized tropoelastin (TE) in LF cultures.
• bFGF exposure led to a corresponding decrease in elastin mRNA levels, indicating transcriptional regulation.
• bFGF reduced elastin promoter activity, confirming its suppressive effect on elastin gene transcription.
• Neutralization of endogenous bFGF with an antibody increased soluble elastin production by LF.

Conclusions:

• Basic fibroblast growth factor (bFGF) suppresses elastin production in lung interstitial fibroblasts at the transcriptional level.
• Both exogenous and endogenous bFGF can inhibit elastin synthesis.
• These findings suggest that bFGF may play a significant role in modulating elastin production during lung development and in chronic inflammatory conditions.