An analysis of the effects of stretch on IGF-I secretion from rat ventricular fibroblasts

Abstract

Mechanical force can induce a number of fundamental short- and long-term responses in myocardium. These include alterations in ECM, activation of cell-signaling pathways, altered gene regulation, changes in cell proliferation and growth, and secretion of a number of peptides and growth factors. It is now known that a number of these autocrine/paracrine factors are secreted from both cardiomyocytes and ventricular cardiac fibroblasts (CFb) in response to stretch. One such substance is IGF-I. IGF-I is an important autocrine/paracrine factor that can regulate physiological or pathophysiological responses, such as hypertrophy. In this study, we addressed the possible effects of mechanical perturbation, biaxial strain, on IGF-I secretion from adult rat CFb. CFb were subjected to either static stretch (3–10%) or cyclic stretch (10%; 0.1–1 Hz) over a 24-h period. IGF-1 secretion from CFb in response to selected stretch paradigms was examined using ELISA to measure IGF-I concentrations in conditioned media. Static stretch did not result in any measurable modulation of IGF-I secretion from CFb. However, cyclic stretch significantly increased IGF-I secretion from CFb in a frequency- and time-dependent manner compared with nonstretched controls. This stretch-induced increase in secretion was relatively insensitive to changes in extracellular [Ca2+] or to block of L-type Ca2+ channels. In contrast, thapsigargin, an inhibitor of sarco(endo)plasmic reticulum Ca2+ ATPase, remarkably decreased stretch-induced IGF-I secretion from CFb. We further show that IGF-I can upregulate mRNA expression of atrial natriuretic peptide in myocytes. In summary, cyclic stretch can significantly increase IGF-I secretion from CFb, and this effect is dependent on a thapsigargin-sensitive pool of intracellular [Ca2+].

Insulin-Like Growth Factor-1 Receptor Identifies a Pool of Human Cardiac Stem Cells With Superior Therapeutic Potential for Myocardial Regeneration

“…27 The function of IGF-1R-positive hCSCs is regulated by both IGF-1 and IGF-2 which exert opposite effects on the fate of these cells. Importantly, cardiomyocytes and fibroblasts surrounding hCSCs have the ability to secrete the IGF-1 and IGF-2 ligand, 28,29 suggesting that a cross-talk occurs within the cardiac niches where myocytes and fibroblasts function as supporting cells. 21,30 These cells may dictate the developmental decision of hCSCs according to the needs of the organ.…”

Regulatory effects of biomechanical strain on the insulin-like growth factor system in human periodontal cells

“…In a study on human osteoblast-like cells, continuous cyclic mechanical strain also caused an increase in IGF1, suggesting that mechanical cell loading alters local expression of growth factors and, thereby, bone formation (Cillo et al, 2000). Similar finding have been reported in other cells such a ventricular fibroblasts, in which cyclic stretch significantly increased the IGF1 secretion in a frequency-and time-dependent manner compared with controls (Hu et al, 2007). In previous immunohistochemical studies, we have demonstrated the presence of IGF2 in the human PDL (Gotz et al, 2006a).…”

Compensatory cellular hypertrophy: the other strategy for tissue homeostasis

“…This change of tension within the epithelium or the geometry of cells can be rather “random” and spread a few cells away, without necessarily having a greater effect on their immediate neighbors. Interestingly, cyclic mechanic stretch has been shown to enhance the hypertrophic growth of mammalian cardiomyocytes or chick skeletal muscle cells [40–42], and several previous reports revealed that the IIS pathway is also involved in mechanical stretch-induced hypertrophy [42, 43]. …”