An analysis of the effects of stretch on IGF-I secretion from rat ventricular fibroblasts.
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 [Ca(2+)] or to block of L-type Ca(2+) channels. In contrast, thapsigargin, an inhibitor of sarco(endo)plasmic reticulum Ca(2+) 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 [Ca(2+)].
Hu
Betty S
BS
Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada.
Landeen
Lee K
LK
Aroonsakool
Nakon
N
Giles
Wayne R
WR
D000818:Animals; D002478:Cells, Cultured; D004548:Elasticity; D005347:Fibroblasts / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D016276:Ventricular Function
D007334:Insulin-Like Growth Factor I