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.

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.

Aberrant expression of G1-phase cell cycle regulators in flat and exophytic adenomas of the human colon

2001 ◽  
Vol 120 (7) ◽  
pp. 1680-1688 ◽  
Author(s):  
Jirina Bartkova ◽  
Minna Thullberg ◽  
Premysl Slezak ◽  
Edgar Jaramillo ◽  
Carlos Rubio ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Human Colon ◽  
Phase Cell ◽  
G1 Phase ◽  
Cell Cycle Regulators ◽  
Aberrant Expression

scholarly journals Interferon-λ1 induces G1 phase cell cycle arrest and apoptosis in gastric carcinoma cells in vitro

2014 ◽  
Vol 32 (1) ◽  
pp. 199-204 ◽  
Author(s):  
ZHITAO GAO ◽  
MOLI ZHU ◽  
YAPING WU ◽  
PAN GAO ◽  
ZHIHAI QIN ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gastric Carcinoma ◽  
Cell Cycle Arrest ◽  
Carcinoma Cells ◽  
Phase Cell ◽  
G1 Phase ◽  
Cycle Arrest

scholarly journals Terminalia bentzoë, a Mascarene Endemic Plant, Inhibits Human Hepatocellular Carcinoma Cells Growth In Vitro via G0/G1 Phase Cell Cycle Arrest

2020 ◽  
Vol 13 (10) ◽  
pp. 303 ◽  
Author(s):  
Nawraj Rummun ◽  
Philippe Rondeau ◽  
Emmanuel Bourdon ◽  
Elisabete Pires ◽  
James McCullagh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Phase Cell ◽  
G1 Phase ◽  
Cytotoxic Activities ◽  
Hepatocellular Carcinoma Cells ◽  
Human Hepatocellular Carcinoma Cells

Tropical forests constitute a prolific sanctuary of unique floral diversity and potential medicinal sources, however, many of them remain unexplored. The scarcity of rigorous scientific data on the surviving Mascarene endemic taxa renders bioprospecting of this untapped resource of utmost importance. Thus, in view of valorizing the native resource, this study has as its objective to investigate the bioactivities of endemic leaf extracts. Herein, seven Mascarene endemic plants leaves were extracted and evaluated for their in vitro antioxidant properties and antiproliferative effects on a panel of cancer cell lines, using methyl thiazolyl diphenyl-tetrazolium bromide (MTT) and clonogenic cell survival assays. Flow cytometry and comet assay were used to investigate the cell cycle and DNA damaging effects, respectively. Bioassay guided-fractionation coupled with liquid chromatography mass spectrometry (MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopic analysis were used to identify the bioactive compounds. Among the seven plants tested, Terminaliabentzoë was comparatively the most potent antioxidant extract, with significantly (p < 0.05) higher cytotoxic activities. T. bentzoë extract further selectively suppressed the growth of human hepatocellular carcinoma cells and significantly halted the cell cycle progression in the G0/G1 phase, decreased the cells’ replicative potential and induced significant DNA damage. In total, 10 phenolic compounds, including punicalagin and ellagic acid, were identified and likely contributed to the extract’s potent antioxidant and cytotoxic activities. These results established a promising basis for further in-depth investigations into the potential use of T. bentzoë as a supportive therapy in cancer management.

scholarly journals Cediranib Induces Apoptosis, G1 Phase Cell Cycle Arrest, and Autophagy in Non-Small-Cell Lung Cancer Cell A549 In Vitro

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Menghuan Guo ◽  
Zhiyuan Liu ◽  
Jing Si ◽  
Jinhua Zhang ◽  
Jin Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
A549 Cells ◽  
Small Cell ◽  
Phase Cell ◽  
G1 Phase ◽  
Small Cell Lung ◽  
Cycle Arrest

Lung cancer remains the leading cause of cancer death worldwide. Late diagnosis, chemoresistance, and metastasis are the main reasons for the high mortality rate of lung cancer. Therefore, the development of other treatments is urgent. Cediranib (CED), a vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, shows promising antitumour activities in various cancers including lung cancer. Here, we explored the effects and the underlying molecular mechanism of CED on non-small-cell lung cancer (NSCLC) cell line A549 cells in vitro. Our results show that CED could inhibit A549 cell proliferation and cloning formation. Meanwhile, G1 phase cell cycle arrest was also found, as featured by the increased proportion of G1 phase cells as well as the reduction of G1 phase relative proteins CDK4/cyclin D1 and CDK2/cyclin E. Moreover, the ratio of LC3-II/LC3-I was elevated significantly in CED-treated groups compared with the controls. Furthermore, the expression of p-Akt, p-P38, p-Erk1/2, and p-mTOR proteins was decreased obviously in the treatment groups. These results suggest that CED could induce apoptosis and G1 phase cell cycle arrest in A549 cells. Meanwhile, CED may induce autophagy through MAPK/Erk1/2 and Akt/mTOR signal pathway in A549 cells.

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