Key result
IGF-1 modulated cardiac fibroblast behavior and gene expression to different degrees depending on whether the cells were isolated from fetal, neonatal, or adult rats.
The response of rat cardiac fibroblasts to IGF-1, including collagen expression and ECM interaction, varies significantly depending on the developmental age of the animal.
Age modulates IGF-1 effects on cardiac fibroblasts; leaves open translation to human fibrosis or remodeling across the lifespan.
The collagenous extracellular matrix (ECM) forms a stress-tolerant network that is essential for proper function of the vertebrate heart. Profound changes have been detected in the interstitial ECM concurrent with developmental and disease processes of the heart. These alterations in either the organization or accumulation of ECM components markedly affect myocardial function. Studies have shown that a number of biochemical factors, including angiotensin II, transforming growth factor-beta, and insulin-like growth factors, modulate collagen expression by heart fibroblasts, however, few studies have examined the differential effects of these factors on fibroblasts from animals of different physiological backgrounds. The present studies were carried out to determine whether cardiac fibroblasts isolated from different aged animals (fetal, neonatal, and adult) have diverse responses to insulin-like growth factor-1 (IGF-1). Fibroblasts isolated from fetal, neonatal, and adult rat hearts were treated with IGF-1, and several downstream responses were measured, including collagen gel contraction, adhesion to ECM, and expression of interstitial collagen and integrins. IGF-1 affected these parameters to different degrees, depending on the age of the animal from which the fibroblasts were isolated. These experiments indicate that IGF-1 is a potent modulator of fibroblast behavior in general; however, significant differences are apparent in the responsiveness of cells to this growth factor depending on the age of the animal of origin. Future experiments will be directed at determining how the in vivo chemical and biomechanical environment affects the response of heart fibroblasts to growth factors such as IGF-1.
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Dı́az-Araya et al. (2003) studied this question. IGF-1 was evaluated on Collagen gel contraction, adhesion to ECM, and expression of interstitial collagen and integrins. IGF-1 modulated cardiac fibroblast behavior and gene expression to different degrees depending on whether the cells were isolated from fetal, neonatal, or adult rats.
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