Enhanced growth of small bowel in transgenic mice expressing human insulin-like growth factor I

Ohneda, Kinuko; Ulshen, M. H.; Fuller, C. Randall; D’Ercole, A. Joseph; Lund, Patricia

doi:10.1053/gast.1997.v112.pm9024298

Cited by 147 publications

(109 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Villus height was measured as described previously. 38 For villin, gelsolin and Ki67 staining, tissue were deparaffinized in xylene for 10 min followed by incubation in serial dilutions of ethanol (100, 95 and 75%) for 5 min each. Following antigen retrieval, sections were incubated for 1 h at room temperature with anti-villin, anti-gelsolin or Ki67 antibodies.…”

Section: Methodsmentioning

confidence: 99%

Actin reorganization as the molecular basis for the regulation of apoptosis in gastrointestinal epithelial cells

et al. 2012

View full text Add to dashboard Cite

The gastrointestinal (GI) epithelium is a rapidly renewing tissue in which apoptosis represents part of the overall homeostatic process. Regulation of apoptosis in the GI epithelium is complex with a precise relationship between cell position and apoptosis. Apoptosis occurs spontaneously and in response to radiation and cytotoxic drugs at the base of the crypts. By contrast, the villus epithelial cells are extremely resistant to apoptosis. The molecular mechanism underlying this loss of function of villus epithelial cells to undergo apoptosis shortly after their exit from the crypt is unknown. In this study we demonstrate for the first time, that deletion of two homologous actin-binding proteins, villin and gelsolin renders villus epithelial cells extremely sensitive to apoptosis. Ultrastructural analysis of the villin-gelsolin À/À double-knockout mice shows an abnormal accumulation of damaged mitochondria demonstrating that villin and gelsolin function on an early step in the apoptotic signaling at the level of the mitochondria. A characterization of functional and ligand-binding mutants demonstrate that regulated changes in actin dynamics determined by the actin severing activities of villin and gelsolin are required to maintain cellular homeostasis. Our study provides a molecular basis for the regulation of apoptosis in the GI epithelium and identifies cell biological mechanisms that couple changes in actin dynamics to apoptotic cell death.

show abstract

Section: Methodsmentioning

confidence: 99%

Actin reorganization as the molecular basis for the regulation of apoptosis in gastrointestinal epithelial cells

et al. 2012

View full text Add to dashboard Cite

show abstract

“…We have previously shown that in human intestinal smooth muscle cells, like skeletal muscle cells and vascular smooth muscle cells, IGF-I activates both the ERK1/2 and PI3K pathways that regulate growth (11,14,24). The particular importance of IGF-I in regulating the growth of intestinal smooth muscle is demonstrated by the hyperplasia that occurs in both intestinal and vascular smooth muscle tissues of transgenic animals overexpressing an IGF-I cDNA (31,48). The pathways mediating intestinal smooth muscle proliferation are likely to play an important role in the setting of Crohn's disease, in which IGF-I expression is upregulated and may contribute to the hyperplasia of smooth muscle that contributes to the formation of intestinal strictures (53).…”

mentioning

confidence: 99%

IGF-I elicits growth of human intestinal smooth muscle cells by activation of PI3K, PDK-1, and p70S6 kinase

Kuemmerle

2003

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Endogenous IGF-I regulates growth of human intestinal smooth muscle cells by jointly activating phosphatidylinositol 3-kinase (PI3K) and ERK1/2. The 70-kDa ribosomal S6 kinase (p70S6 kinase) is a key regulator of cell growth activated by several independently regulated kinases. The present study characterized the role of p70S6 kinase in IGF-I-induced growth of human intestinal smooth muscle cells and identified the mechanisms of p70S6 kinase activation. IGF-I-induced growth elicited via either the PI3K or ERK1/2 pathway required activation of p70S6 kinase. IGF-I elicited concentration-dependent activation of PI3K, 3-phosphoinositide-dependent kinase-1 (PDK-1), and p70S6 kinase that was sequential and followed similar time courses. IGF-I caused time-dependent and concentration-dependent phosphorylation of p70S6 kinase on Thr421/Ser424, Thr389, and Thr229 that paralleled p70S6 kinase activation. p70S6 kinase(Thr421/Ser424) phosphorylation was PI3K dependent and PDK-1 independent, whereas p70S6 kinase(Thr389) and p70S6 kinase(Thr229) phosphorylation and p70S6 kinase activation were PI3K dependent and PDK-1 dependent. IGF-I elicited sequential Akt(Ser308), Akt(Ser473), and mammalian target of rapamycin(Ser2448) phosphorylation; however, transfection of muscle cells with kinase-inactive Akt1(K179M) showed that these events were not required for IGF-I to activate p70S6 kinase and stimulate proliferation of human intestinal muscle cells.

show abstract

“…The central role of IGF-I in the regulation of smooth muscle cell growth in both the normal and pathologic states is manifested by the hyperplasia of intestinal and vascular smooth muscle in transgenic animals overexpressing a human IGF-I cDNA (4,5). The effects of IGF-I are modulated by IGF-binding proteins.…”

mentioning

confidence: 99%

Insulin-like Growth Factor-binding Protein-5 (IGFBP-5) Stimulates Growth and IGF-I Secretion in Human Intestinal Smooth Muscle by Ras-dependent Activation of p38 MAP Kinase and Erk1/2 Pathways

Kuemmerle¹,

Zhou²

2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Enhanced growth of small bowel in transgenic mice expressing human insulin-like growth factor I

Cited by 147 publications

References 3 publications

Actin reorganization as the molecular basis for the regulation of apoptosis in gastrointestinal epithelial cells

Actin reorganization as the molecular basis for the regulation of apoptosis in gastrointestinal epithelial cells

IGF-I elicits growth of human intestinal smooth muscle cells by activation of PI3K, PDK-1, and p70S6 kinase

Insulin-like Growth Factor-binding Protein-5 (IGFBP-5) Stimulates Growth and IGF-I Secretion in Human Intestinal Smooth Muscle by Ras-dependent Activation of p38 MAP Kinase and Erk1/2 Pathways

Contact Info

Product

Resources

About