scholarly journals Platelet-Derived Growth Factor Blocks the Cell-Cycle Transition from the G0 to G1 Phase in Subcultured Angiogenic Endothelial Cells in Rat Thoracic Aorta.

1997 ◽  
Vol 74 (4) ◽  
pp. 303-311 ◽  
Author(s):  
Ikuko Kimura ◽  
Hiroshi Tsuneki ◽  
Motonori Okabe ◽  
Masaru Ogasawara
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Thoracic Aorta ◽  
Platelet Derived Growth Factor ◽  
G1 Phase ◽  
Rat Thoracic Aorta ◽  
Cell Cycle Transition

scholarly journals Cell surface thrombospondin is functionally essential for vascular smooth muscle cell proliferation

1988 ◽  
Vol 106 (2) ◽  
pp. 415-422 ◽  
Author(s):  
RA Majack ◽  
LV Goodman ◽  
VM Dixit
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Growth Factor ◽  
Cell Surface ◽  
Vascular Smooth Muscle ◽  
Cell Number ◽  
Platelet Derived Growth Factor ◽  
G1 Phase ◽  
Detectable Effect

Thrombospondin (TS) is an extracellular glycoprotein whose synthesis and secretion by vascular smooth muscle cells (SMC) is regulated by platelet-derived growth factor. We have used a panel of five monoclonal antibodies against TS to determine an essential role for thrombospondin in the proliferation of cultured rat aortic SMC. All five monoclonal antibodies inhibited SMC growth in 3-d and extended cell number assays; the growth inhibition was specific for anti-TS IgG. The effects of one antibody (D4.6) were examined in detail and were found to be reversable and dose dependent. Cells treated with D4.6 at 50 micrograms/ml (which resulted in a greater than 60% reduction in cell number at day 8) were morphologically identical to control cells. D4.6-treated SMC were analyzed by flow cytofluorimetry and were found to be arrested in the G1 phase of the cell cycle. To determine a possible cellular site of action of TS in cell growth, SMC were examined by immunofluorescence using a polyclonal antibody against TS. TS was observed diffusely bound to the cell surface of serum- or platelet-derived growth factor-treated cells. The binding of TS to SMC was abolished in the presence of heparin, which prevents the binding of TS to cell surfaces and inhibits the growth of SMC. Monoclonal antibody D4.6, like heparin, largely abolished cell surface staining of TS but had no detectable effect on the cellular distribution of fibronectin. These results were corroborated by metabolic labeling experiments. We conclude that cell surface-associated TS is functionally essential for the proliferation of vascular SMC, and that this requirement is temporally located in the G1 phase of the cell cycle. Agents that perturb the interaction of TS with the SMC surface, such as heparin, may inhibit SMC proliferation in this manner.

scholarly journals Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yuehong Ma ◽  
Ling Fang ◽  
Rui Zhang ◽  
Peng Zhao ◽  
Yafeng Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Lupus Nephritis ◽  
Renal Fibrosis ◽  
Platelet Derived Growth Factor ◽  
Phase Cell ◽  
G1 Phase ◽  
Cell Cycle Regulators ◽  
Subunit B

Objectives. Most patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN) with severe kidney manifestations. Renal fibrosis can be primarily attributed to overproliferation of mesangial cells (MCs), which are subject to drug treatment. Nevertheless, the detailed mechanisms remain elusive. We sought to identify the effect of cyclophosphamide (CTX), a drug commonly used for LN treatment, on MC proliferation and explore its underlying mechanisms. Material/Methods. Cell proliferation and fibrosis in mouse kidney tissues were determined by histopathology staining techniques. Flow cytometry was used for cell cycle analysis. Cell cycle regulators were examined in vitro following treatment of immortalized human MCs with platelet-derived growth factor subunit B (PDGF-B). Quantitative real-time PCR and western blot analyses were used to measure the mRNA and protein levels of candidate cell cycle regulators, respectively. Results. CTX inhibited cell overproliferation induced by platelet-derived growth factor subunit B in vitro and in vivo. CTX (40 mg/l) was sufficient to induce G0/G1 phase cell cycle arrest. CTX treatment downregulated many critical cell cycle regulators including cyclins and cyclin-dependent kinases but upregulated cyclin-dependent kinase inhibitors. Additionally, CTX-treated samples showed significantly reduced fibrosis, as indicated by lower expression of interleukin-1β and α-smooth muscle actin. Conclusion. CTX inhibits proliferation of MCs by modulating cell cycle regulator and therefore arresting them at G1 phase. CTX treatment significantly alleviates the severity of renal fibrosis. These findings provide novel insights into the mechanisms by which CTX affects LN.

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