Evidence for a functional role of endogenously produced somatomedinlike peptides in the regulation of DNA synthesis in cultured human fibroblasts and porcine smooth muscle cells.

Abstract

Cultured porcine aortic smooth muscle cells and human fibroblasts produce somatomedinlike peptides and secrete them into the surrounding microenvironment. This production has been linked to their ability to replicate. The objective of this study was to determine if a specific anti-somatomedin-C (Sm-C) monoclonal antibody that binds the somatomedinlike peptides could inhibit replication by porcine aortic smooth muscle cells and human fibroblasts. To determine if the antibody could inhibit the effect of endogenously produced somatomedinlike peptide, increasing concentrations of antibody were co-incubated with platelet-derived growth factor, a known stimulant of somatomedinlike peptide secretion, and Sm-C-deficient plateletpoor plasma.

Expression and function of receptors for insulin-like growth factor-I and insulin in human coronary artery smooth muscle cells

“…In human aortic VSMCs, IGF-I at 10 −9 mol/l also stimulated DNA synthesis [20,42,43]. Evidence also exists that IGF-I plays a functional role in the regulation of DNA synthesis, assayed by [ 3 H]thymidine incorporation, in cultured porcine and rat aortic and coronary smooth muscle cells [11,13,25,35,36,44]. In our study, glucose accumulation into HCASMCs was also significantly stimulated by IGF-I in low concentration.…”

“…In atherosclerotic vascular lesions and restenosis after percutaneous transluminal coronary angioplasty, proliferation of vascular smooth muscle cells (VSMCs) takes place [6,7]. IGF-I has been reported to be a chemoattractant factor and to regulate metabolism, cell proliferation, differentiation and survival in VSMCs of animal origin [8][9][10][11][12]. Although several reports have documented the expression of IGF-I and its receptor (IGF-IR) in VSMCs from bovine [13][14][15], porcine [16] and rat [17,18], little is known about the expression and function of insulin receptor (IR) and IGF-IR in human VSMCs [19][20][21].…”

Transforming growth factors and the regulation of cell proliferation

“…Concurrent investigalions of other growth factors, including platelet-derived growth factor (PDGF) [23], insulin-like growth factor-1 (IGF-1) [24] and interleukin-2 (IL-2) [25] have shown that autocrine stimulation of proliferation should be considered a general phenomenon of most cells. Thus, the autocrine hypothesis is no longer regarded as an abnormal process occurring only in transformed cells leading to excessive( proliferation; rather it is believed to be an important function of the regulation of normal cell growth.…”

Insulin-like growth factor I in cultured rat astrocytes: expression of the gene, and receptor tyrosine kinase.

“…A formal proof for an involvement of the endogenously produced IGF I in stimulation of astroglial cell growth in culture would require that cell replication be arrested by addition of specific antibodies to IGF I or its receptor. Evidence for autocrine or paracrine mechanisms in growth regulation by IGF I has been obtained with other cell types, such as cultured human fibroblasts and porcine smooth muscle cells (Clemmons and Van Wyk, 1985), and rat chondrocytes in vivo (Nilsson et al, 1986). In these two studies, production of IGF I was found to be stimulated by platelet-derived growth factor and growth hormone respectively.…”