Glucose Regulation of Thrombospondin and Its Role in the Modulation of Smooth Muscle Cell Proliferation

Maile, Laura A.; Allen, Lee; Hanzaker, Christopher F.; Gollahon, Katherine A.; Dunbar, P. Rod; Clemmons, David R.

doi:10.1155/2010/617052

Cited by 18 publications

(17 citation statements)

References 37 publications

(60 reference statements)

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“…mesangial cells, and vascular smooth muscle cells contribute to the cardiovascular and nephritic complications of diabetes (Neumann et al 2002, Tokudome et al 2004, Maile et al 2010, and ERK1/2 activation has been linked to high glucose-induced fibrosis (Tang et al 2007). Consistent with these previous reports, high glucose presently increased cell proliferation and affected the expression of ECM-related genes in cardiac fibroblasts by modulating ERK activities.…”

Section: Discussionsupporting

confidence: 75%

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

Song¹,

Kim²,

Kim³

et al. 2013

Journal of Molecular Endocrinology

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This study examined whether IGF-binding protein 5 (IGFBP5) is involved in the high glucoseinduced deteriorating effects in cardiac cells. Cardiac fibroblasts and cardiomyocytes were isolated from the hearts of 1-to 3-day-old Sprague Dawley rats. Treatment of fibroblasts with 25 mM glucose increased the number of cells and the mRNA levels of collagen III, matrix metalloproteinase 2 (MMP2), and MMP9. High glucose increased ERK1/2 activity, and the ERK1/2 inhibitor PD98059 suppressed high glucose-mediated fibroblast proliferation and increased collagen III mRNA levels. Whereas high glucose increased both mRNA and protein levels of IGFBP5 in fibroblasts, high glucose did not affect IGFBP5 protein levels in cardiomyocytes. The high glucose-induced increase in IGFBP5 protein levels was inhibited by PD98059 in fibroblasts. While recombinant IGFBP5 increased ERK phosphorylation, cell proliferation, and the mRNA levels of collagen III, MMP2, and MMP9 in fibroblasts, IGFBP5 increased c-Jun N-terminal kinase phosphorylation and induced apoptosis in cardiomyocytes. The knockdown of IGFBP5 inhibited high glucose-induced cell proliferation and collagen III mRNA levels in fibroblasts. Although high glucose increased IGF1 levels, IGF1 did not increase IGFBP5 levels in fibroblasts. The hearts of Otsuka Long-Evans Tokushima Fatty rats and the cardiac fibroblasts of streptozotocin-induced diabetic rats showed increased IGFBP5 expression. These results suggest that IGFBP5 mediates high glucose-induced profibrotic effects in cardiac fibroblasts.

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Section: Discussionsupporting

confidence: 75%

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

Song¹,

Kim²,

Kim³

et al. 2013

Journal of Molecular Endocrinology

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“…1C) (Rebres et al, 2005). This interaction may require an unidentified trypsin-sensitive protein (X) to mediate cell-cell adhesion, but the potential should be considered that this cell-cell interaction and homotypic binding of proteolytically shed CD47 IgV domain (Maile et al, 2010) or CD47 in exosomes (Kaur et al, 2014b) to cell surface CD47 could elicit CD47 signal transduction. However, direct evidence for CD47-CD47 binding and signaling resulting from homotypic CD47 binding is lacking.…”

Section: Cd47 Structure and Interactionsmentioning

confidence: 99%

CD47 signaling pathways controlling cellular differentiation and responses to stress

Soto-Pantoja

Kaur

Roberts

2015

Critical Reviews in Biochemistry and Molecular Biology

153

166

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CD47 is a widely expressed integral membrane protein that serves as the counter-receptor for the inhibitory phagocyte receptor signal-regulatory protein-α (SIRPα) and as a signaling receptor for the secreted matricellular protein thrombospondin-1. Recent studies employing mice and somatic cells lacking CD47 have revealed important pathophysiological functions of CD47 in cardiovascular homeostasis, immune regulation, resistance of cells and tissues to stress, and chronic diseases of aging including cancer. With the emergence of experimental therapeutics targeting CD47, a more thorough understanding of CD47 signal transduction is essential. CD47 lacks a substantial cytoplasmic signaling domain, but several cytoplasmic binding partners have been identified, and lateral interactions of CD47 with other membrane receptors play important roles in mediating signaling resulting from the binding of thrombospondin-1. This review addresses recent advances in identifying the lateral binding partners, signal transduction pathways, and downstream transcription networks regulated through CD47 in specific cell lineages. Major pathways regulated by CD47 signaling include calcium homeostasis, cyclic nucleotide signaling, nitric oxide and hydrogen sulfide biosynthesis and signaling, and stem cell transcription factors. These pathways and other undefined proximal mediators of CD47 signaling regulate cell death and protective autophagy responses, mitochondrial biogenesis, cell adhesion and motility, and stem cell self-renewal. Although thrombospondin-1 is the best characterized agonist of CD47, the potential roles of other members of the thrombospondin family, SIRPα and SIRPγ binding, and homotypic CD47 interactions as agonists or antagonists of signaling through CD47 should also be considered.

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“…56,57 In myeloid cells, SIRP-a phosphorylation has been demonstrated in the absence of CD47. 55 Our data indicate that in nonmyeloid cells, TSP1 stimulates the phosphorylation of SIRP-a and its downstream effector SHP1 through a process that may depend on interaction with CD47.…”

Section: J Am Soc Nephrol 25: 1171-1186 2014 Tsp1-sirp-a Signaling Rmentioning

confidence: 99%

Thrombospondin-1 Activation of Signal-Regulatory Protein-α Stimulates Reactive Oxygen Species Production and Promotes Renal Ischemia Reperfusion Injury

Yao¹,

Rogers²,

Csányi³

et al. 2014

Journal of the American Society of Nephrology

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Ischemia reperfusion injury (IRI) causes tissue and organ injury, in part, through alterations in tissue blood flow and the production of reactive oxygen species. The cell surface receptor signal-regulatory protein-a (SIRP-a) is expressed on inflammatory cells and suppresses phagocytosis, but the function of SIRP-a in IRI has not been determined. We reported previously that the matricellular protein thrombospondin-1 is upregulated in IRI. Here, we report a novel interaction between thrombospondin-1 and SIRP-a on nonphagocytic cells. In cell-free experiments, thrombospondin-1 bound SIRP-a. In vascular smooth muscle cells and renal tubular epithelial cells, treatment with thrombospondin-1 led to phosphorylation of SIRP-a and downstream activation of Src homology domain 2-containing phosphatase-1. Thrombospondin-1 also stimulated phosphorylation of p47 phox (an organizer subunit for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1/2) and increased production of superoxide, both of which were abrogated by knockdown or antibody blockade of SIRP-a. In rodent aortic rings, treatment with thrombospondin-1 increased the production of superoxide and inhibited nitric oxidemediated vasodilation in a SIRP-a-dependent manner. Renal IRI upregulated the thrombospondin-1-SIRP-a signaling axis and was associated with increased superoxide production and cell death. A SIRP-a antibody that blocks thrombospondin-1 activation of SIRP-a mitigated the effects of renal IRI, increasing blood flow, suppressing production of reactive oxygen species, and preserving cellular architecture. A role for CD47 in SIRP-a activation in these pathways is also described. Overall, these results suggest that thrombospondin-1 binding to SIRP-a on nonphagocytic cells activates NADPH oxidase, limits vasodilation, and promotes renal IRI.

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Glucose Regulation of Thrombospondin and Its Role in the Modulation of Smooth Muscle Cell Proliferation

Cited by 18 publications

References 37 publications

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

CD47 signaling pathways controlling cellular differentiation and responses to stress

Thrombospondin-1 Activation of Signal-Regulatory Protein-α Stimulates Reactive Oxygen Species Production and Promotes Renal Ischemia Reperfusion Injury

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