Dataset Information

Osteoprotegerin promotes islet ? cell proliferation in intrauterine growth retardation rats through the PI3K/AKT/FoxO1 pathway.

ABSTRACT: Osteoprotegerin (OPG) is a critical factor involved in bone metabolism. The level of OPG is increased in the serum of diabetic patients; however, there is no consensus in prior studies on the role of OPG in regulating the function of islet ? cells. A rat model of intrauterine growth retardation (IUGR) was established in the present study to investigate whether OPG could enhance the proliferation of ? cells; and an in vitro culture model of rat islet ? cell line INS-1 was used, to confirm the effect of OPG supplementation and reveal the possible mechanism. The results showed that endogenous OPG expression was reduced and normal proliferation of ? cells was impaired in the IUGR islets. Exogenous supplement of OPG restored ? cell proliferation to an extent in the IUGR rats, possibly associated with regulation of the PI3K/AKT/FoxO1 signalling, as evidenced by the changes of protein expression in the pathway. Furthermore, treating rat islet INS-1 cells with a PI3K inhibitor, LY294002, blunted the effects of OPG supplement in promoting cell cycle and suppressing cell apoptosis. Taken together, the present work demonstrated that OPG supplementation could improve the proliferation of islet ? cells in IUGR, and the PI3K/AKT/FoxO1 pathway is involved in the underlying mechanism.

SUBMITTER: Tang S

PROVIDER: S-EPMC6949609 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Osteoprotegerin promotes islet β cell proliferation in intrauterine growth retardation rats through the PI3K/AKT/FoxO1 pathway.

Tang Shi S Xin Ying Y Yang Min M Zhang Dan D Xu Chunzhuo C

International journal of clinical and experimental pathology 20190601 6

Osteoprotegerin (OPG) is a critical factor involved in bone metabolism. The level of OPG is increased in the serum of diabetic patients; however, there is no consensus in prior studies on the role of OPG in regulating the function of islet β cells. A rat model of intrauterine growth retardation (IUGR) was established in the present study to investigate whether OPG could enhance the proliferation of β cells; and an <i>in vitro</i> culture model of rat islet β cell line INS-1 was used, to confirm ...[more]

PMID: 31934060

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Project description:Proliferation is one of the significant hallmarks of gallbladder cancer, which is a relatively rare but fatal malignance. Aim of this study was to examine the biological impact and molecular mechanism of the candidate hub-gene on the proliferation and tumorigenesis of gallbladder cancer. We analyzed the differentially expressed genes and the correlation between these genes with MKI67, and showed that KIF11 is one of the major upregulated regulators of proliferation in gallbladder cancer (GBC). The Gene Ontology, Gene Sets Enrichment Analysis and KEGG Pathway analysis indicated that KIF11 may promote GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. Gain-of-function and loss-of-function assay demonstrated that KIF11 regulated GBC cell cycle and cancer cell proliferation in vitro. GBC cells exhibited G2M phase cell cycle arrest, cell proliferation and clone formation ability reduction after treatment with Monastrol, a specific inhibitor of KIF11. Xenograft model showed that KIF11 promotes GBC growth in vivo. Rescue experiments showed that KIF11-induced GBC cell proliferation dependented on ERBB2/PI3K/AKT pathway. Moreover, we found that H3K27ac signals are enriched among the promoter region of KIF11 in the UCSC Genome Browser Database. Differentially expressed analysis showed that EP300, a major histone acetyltransferase modifying H3K27ac signal, is highly expressed in gallbladder cancer and correlation analysis illustrated that EP300 is positively related with KIF11 in almost all the cancer types. We further found that KIF11 was significantly downregulated in a dose-dependent and time-dependent manner after histone acetylation inhibitor treatment. The present results highlight that high KIF11 expression promotes GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. The findings may help deepen our understanding of mechanism underlying GBC cancer development and development of novel diagnostic and therapeutic target.

Dataset Information

Osteoprotegerin promotes islet ? cell proliferation in intrauterine growth retardation rats through the PI3K/AKT/FoxO1 pathway.

Publications

Osteoprotegerin promotes islet β cell proliferation in intrauterine growth retardation rats through the PI3K/AKT/FoxO1 pathway.

Similar Datasets

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