Role of IGF-1 pathway in lung fibroblast activation

被引:74
作者
Hung, Chi F. [1 ]
Rohani, Maryam G. [1 ]
Lee, Sung-soon [1 ]
Chen, Peter [1 ]
Schnapp, Lynn M. [1 ]
机构
[1] Univ Washington, Div Pulm & Crit Care Med, Dept Med, Ctr Lung Biol, Seattle, WA 98109 USA
来源
RESPIRATORY RESEARCH | 2013年 / 14卷
关键词
Fibroblasts; IGF; Fibrosis; GROWTH-FACTOR-I; SMOOTH MUSCLE ACTIN; RESPIRATORY-DISTRESS-SYNDROME; PULMONARY-FIBROSIS; BINDING PROTEIN-3; INSULIN; MYOFIBROBLAST; CELLS; PROLIFERATION; EXPRESSION;
D O I
10.1186/1465-9921-14-102
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
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 alpha 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-beta on expression of markers of myofibroblast activation in vitro, including alpha SMA, collagen alpha 1, type 1, collagen alpha 1, type III, and TGF beta expression. Results: After bleomycin injury, we found decreased number of alpha SMA-GFP + cells in A12 treated mice, validated by alpha SMA immunofluorescent staining. We found that IGF-1, alone or in combination with TGF-beta, did not affect alpha 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 alpha 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 alpha SMA stress fiber organization in mouse lung fibroblasts.
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页数:11
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