Nephro-protective effect of granulocyte colony-stimulating factor in streptozotocin induced diabetic rats

Background. We previously reported that the granulocyte colony stimulating factor (G-CSF) ameliorated hepatic steatosis with the enhancement of β-oxidation-related gene expression. However, the mechanisms underlying this process remain unclear. This study aimed to determine whether the improvement of hepatic steatosis by G-CSF was associated with autophagy in a rat model of diabetes. Methods. Eight rats were fed a standard diet, and 16 rats were fed high-fat diet (HFD) for 5 weeks. All HFD-fed rats were then injected with streptozotocin (STZ). One week later, HFD rats injected with STZ were randomly treated with either G-CSF (200 μg/kg/day; diabetes mellitus (DM)/G-CSF) or saline (DM/saline) for 5 consecutive days. Four weeks later, serum biochemical and histology analyses were conducted. The expression of autophagy-associated proteins was determined by Western blotting. The mRNA expression of β-oxidation-related genes was determined by quantitative real-time polymerase chain reaction. HepG2 cells were cultured under high glucose (HG) conditions with G-CSF treatment, followed by Oil Red O staining for quantification of lipids. Results. Histological analysis showed lower lipid accumulation in the DM/G-CSF group than in the DM/saline-treated rats. Protein levels of LC3 and beclin-1 were higher, and those of p62 were lower in the DM/G-CSF rats than in the DM/saline-treated rats. The mRNA expression of β-oxidation-related genes was higher in DM/G-CSF rats than in the DM/saline-treated rats. Quantification of lipid levels in HepG2 cells cultured with HG and G-CSF treatment revealed no significant differences. Conclusions. Our data suggested that G-CSF potentially improves hepatic steatosis and autophagy in the liver of diabetic rats.

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Protective Effect of Granulocyte Colony-stimulating Factor on Intracerebral Hemorrhage in Rat

Neurochemical Research ◽

10.1007/s11064-008-9911-6 ◽

2009 ◽

Vol 34 (7) ◽

pp. 1317-1323 ◽

Cited By ~ 12

Author(s):

Lei Zhang ◽

Xi-Ji Shu ◽

Hong-Yan Zhou ◽

Wei Liu ◽

Ying Chen ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Protective Effect ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor

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The Protective Effect of Granulocyte Colony-Stimulating Factor on Endometrium and Ovary in a Rat Model of Diabetes Mellitus

Gynecologic and Obstetric Investigation ◽

10.1159/000363239 ◽

2014 ◽

Vol 78 (2) ◽

pp. 94-100 ◽

Cited By ~ 10

Author(s):

Halil Gursoy Pala ◽

Emel Ebru Pala ◽

Burcu Artunc Ulkumen ◽

Huseyin Aktug ◽

Altug Yavasoglu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Protective Effect ◽

Rat Model ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor

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Granulocyte colony-stimulating factor attenuates oxidative stress–induced apoptosis in vascular endothelial cells and exhibits functional and morphologic protective effect in oxygen-induced retinopathy

Blood ◽

10.1182/blood-2010-05-286963 ◽

2011 ◽

Vol 117 (3) ◽

pp. 1091-1100 ◽

Cited By ~ 36

Author(s):

Hiroshi Kojima ◽

Atsushi Otani ◽

Akio Oishi ◽

Yukiko Makiyama ◽

Satoko Nakagawa ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Protective Effect ◽

Vascular Endothelial Cells ◽

Umbilical Vein ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Oxygen Induced Retinopathy ◽

Induced Apoptosis ◽

Stimulating Factor

Abstract Granulocyte colony-stimulating factor (G-CSF) is a known hematopoietic glycoprotein, and recent studies have revealed that G-CSF possesses other interesting properties. Oxidative stress is involved in many diseases, such as atherosclerosis, heart failure, myocardial infarction, Alzheimer disease, and diabetic retinopathy. This study was designed to examine whether G-CSF has a protective effect on endothelial cells against oxidative stress and to investigate whether G-CSF has a therapeutic role in ischemic vascular diseases. Expression of G-CSF (P < .01) and G-CSF receptor (P < .05) mRNA in human retinal endothelial cells (HRECs) was significantly up-regulated by oxidative stress. Treatment with 100 ng/mL G-CSF significantly reduced H2O2-induced apoptosis in HRECs from 61.7% to 41.4% (P < .05). Akt was phosphorylated in HRECs by G-CSF addition, and LY294002, a PI3K inhibitor, significantly attenuated the antiapoptotic effect of G-CSF (by 44.1%, P < .05). The rescue effect was also observed in human umbilical vein endothelial cells. In mouse oxygen-induced retinopathy model, G-CSF significantly reduced vascular obliteration (P < .01) and neovascular tuft formation (P < .01). G-CSF treatment also clearly rescued the functional and morphologic deterioration of the neural retina. A possibility of a novel therapeutic strategy for ischemic diseases through attenuating vascular regression using G-CSF was proposed.

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