Role of IGF-1 pathway in lung fibroblast activation.

ABSTRACT:

Background

IGF-1 is elevated in pulmonary fibrosis and acute lung injury, where fibroblast activation is a prominent feature. We previously demonstrated that blockade of IGF pathway in murine model of lung fibrosis improved outcome and decreased fibrosis. We now expand that study to examine effects of IGF pathway on lung fibroblast behaviors that could contribute to fibrosis.

Methods

We first examined mice that express ?SMA promoter upstream of GFP reporter treated with A12, a blocking antibody to IGF-1 receptor, after bleomycin induced lung injury. We then examined the effect of IGF-1 alone, or in combination with the pro-fibrotic cytokine TGF? on expression of markers of myofibroblast activation in vitro, including ?SMA, collagen ?1, type 1, collagen ?1, type III, and TGF? expression.

Results

After bleomycin injury, we found decreased number of ?SMA-GFP?+?cells in A12 treated mice, validated by ?SMA immunofluorescent staining. We found that IGF-1, alone or in combination with TGF-?, did not affect ?SMA RNA expression, promoter activity, or protein levels when fibroblasts were cultured on stiff substrate. IGF-1 stimulated Col1a1 and Col3a1 expression on stiff substrate. In contrast, IGF-1 treatment on soft substrate resulted in upregulation of ?SMA gene and protein expression, as well as Col1a1 and Col3a1 transcripts. In conclusion, IGF-1 stimulates differentiation of fibroblasts into a myofibroblast phenotype in a soft matrix environment and has a modest effect on ?SMA stress fiber organization in mouse lung fibroblasts.

SUBMITTER: Hung CF 

PROVIDER: S-EPMC3840605 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature