2.IGF-1R/β-catenin signaling axis is involved in type 2 diabetic osteoporosis.
Zhi-Da ZHANG ; Hui REN ; Wei-Xi WANG ; Geng-Yang SHEN ; Jin-Jing HUANG ; Mei-Qi ZHAN ; Jing-Jing TANG ; Xiang YU ; Yu-Zhuo ZHANG ; De LIANG ; Zhi-Dong YANG ; Xiao-Bing JIANG
Journal of Zhejiang University. Science. B 2019;20(10):838-848
Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.
Aged
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Animals
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Bone Density
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Diabetes Mellitus, Experimental/complications*
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Diabetes Mellitus, Type 2/complications*
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Female
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Humans
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Male
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Middle Aged
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Osteoporosis/etiology*
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Rats
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Receptor, IGF Type 1/physiology*
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Signal Transduction
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Streptozocin
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beta Catenin/physiology*
4.Experimental study on effect of er'zhi tiangui granule in improving quality of oocyte and its correlation with level of insulin-like growth factor-1R mRNA expression in ovary of mice.
Fang LIAN ; Zhen-gao SUN ; Lin MU
Chinese Journal of Integrated Traditional and Western Medicine 2006;26(5):431-434
OBJECTIVETo explore the mechanism of Er'zhi Tiangui Granule (ETG) in improving the quality of oocyte.
METHODSNinety mice were randomly divided into 6 groups. The number of high-quality oocytes was comparatively observed in the 1st experimental group and the 1st control group; the embryonic cleavage rate was observed in the 2nd experimental group and the 2nd control group and the quantity of insulin-like growth factor-1R mRNA (IGF-1R mRNA) expression in ovarian granular cells was determined by using in situ hybridization in the 3rd experimental group and the 3rd control group.
RESULTSThe high-quality oocytes rate, the embryonic cleavage rate and the quantity of IGF-1R mRNA expression in the three paired groups was (78 +/- 8)% vs (71 +/- 5)%, (88 +/- 3)% vs (83 +/- 5)%, 0.4890 +/- 0.0454 vs 0.4439 +/- 0.0283, respectively. The difference between the experimental groups to the respective control groups was significant (all P < 0.05), and positive correlation was shown between the high-quality oocytes rate and the quantity of IGF-1R mRNA expression.
CONCLUSIONThe mechanism of ETG in improving the quality of oocyte may be related with the elevation of IGF-1R mRNA level in ovarian granular cells.
Animals ; Cleavage Stage, Ovum ; physiology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression ; Male ; Mice ; Oocytes ; drug effects ; physiology ; Ovary ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Receptor, IGF Type 1 ; biosynthesis ; genetics
5.The potential role of IGF-I receptor mRNA in rats with diabetic retinopathy.
Hongyu KUANG ; Wei ZOU ; Dan LIU ; Rongxing SHI ; Lihua CHENG ; Huiqing YIN ; Xiaomin LIU
Chinese Medical Journal 2003;116(3):478-480
OBJECTIVETo evaluate the potential role of insulin-like growth factor-1 receptor mRNA (IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.
METHODSA diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.
RESULTSWeak expression of IGF-IR mRNA (5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P < 0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.
CONCLUSIONIncreased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.
Animals ; Blood Glucose ; analysis ; Diabetic Retinopathy ; etiology ; Glycated Hemoglobin A ; analysis ; Insulin-Like Growth Factor I ; physiology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Receptor, IGF Type 1 ; genetics ; Retina ; metabolism ; pathology
6.Effects of insulin-like growth factor 1 receptor and its inhibitor AG1024 on the progress of lung cancer.
Yan-hong WEI ; He-xiao TANG ; Yong-de LIAO ; Sheng-ling FU ; Li-qiang XU ; Guang CHEN ; Chao ZHANG ; Sheng JU ; Zhao-guo LIU ; Liang-kun YOU ; Li YU ; Sheng ZHOU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2015;35(6):834-841
The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the effects of IGF-1R and its inhibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues (n=198). Western blotting was used to determine the expressions of IGF-1 and phosphorylated IGF-1R (p-IGF-1R) in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p-IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF-1+AG1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels. It was concluded that IGF-1 and IGF inhibitor AG1024 promotes lung cancer progression.
Adult
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Aged
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Animals
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Carcinoma, Non-Small-Cell Lung
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metabolism
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pathology
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Cell Proliferation
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Disease Models, Animal
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Disease Progression
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Female
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Humans
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Insulin-Like Growth Factor I
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metabolism
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Lung Neoplasms
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metabolism
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pathology
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Male
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Mice
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Middle Aged
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Receptor, IGF Type 1
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antagonists & inhibitors
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physiology
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Tyrphostins
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pharmacology