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Vitamin D regulates contractile profile in human uterine myometrial cells via NF-?B pathway.

ABSTRACT: Infection triggers inflammation that, in turn, enhances the expression of contractile-associated factors in myometrium and increases the risk of preterm delivery. In this study, we assessed vitamin D regulation of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NF?B pathway proteins in human uterine myometrial smooth muscle (UtSM) cells that were cultured in an inflammatory environment.Inflammatory environment was simulated for UtSM cells by coculturing them with monocyte lineage (THP1) cells. We measured the expression of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NF?B pathway proteins in UtSM cells that were cultured with THP1 cells in the presence and absence of vitamin D by real time polymerase chain reaction and Western blot analysis.Monocytes secreted monocyte inflammatory protein-1? and -1?, interleukin (IL)-1? and 6, and tumor necrosis factor-? into the conditioned medium. In the UtSM cells that had been cocultured with THP1 cells, there was a significant (P < .05) increase in the expression of inflammatory markers IL-1?, -6, and -13 and tumor necrosis factor-?; the contractile-associated factors connexin-43, Cox-2, and prostaglandin F2? receptor; the estrogen receptor ?, and progesterone receptors A and B. Vitamin D treatment of cocultures decreased (P < .05) the expression of inflammatory markers and contractile-associated factors in UtSM cells. Similarly, vitamin D decreased estrogen receptor ? and progesterone receptors A-to-B ratio in UtSM cells that were cocultured with THP1 cells. In addition, vitamin D treatment significantly (P < .05) decreased monocyte-induced p-I?B? in cytosol and NF?B-p65 in the nucleus and increased I?B? in cytosol in UtSM cells.Our results suggest that vitamin D treatment decreases inflammation-induced cytokines and contractile-associated factors in the uterine myometrial smooth muscle cells through the NF?B pathway.

SUBMITTER: Thota C

PROVIDER: S-EPMC3972355 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Vitamin D regulates contractile profile in human uterine myometrial cells via NF-κB pathway.

Thota Chandrasekhar C Laknaur Archana A Farmer Takeisha T Ladson Gwinnett G Al-Hendy Ayman A Ismail Nahed N

American journal of obstetrics and gynecology 20131118 4

<h4>Objective</h4>Infection triggers inflammation that, in turn, enhances the expression of contractile-associated factors in myometrium and increases the risk of preterm delivery. In this study, we assessed vitamin D regulation of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NFκB pathway proteins in human uterine myometrial smooth muscle (UtSM) cells that were cultured in an inflammatory environment.<h4>Study design</h4>Inflammatory environment was simula ...[more]

PMID: 24262718

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Project description:Glioblastoma (GBM) is one of the most lethal primary brain tumor with a poor median survival less than 15 months. Despite the development of the clinical strategies over the decades, the outcomes for GBM patients remain dismal due to the strong proliferation and invasion ability and the acquired resistance to radiotherapy and chemotherapy. Therefore, developing new biomarkers and therapeutic strategies targeting GBM is in urgent need. In this study, gene expression datasets and relevant clinical information were extracted from public cancers/glioma datasets, including TCGA, GRAVENDEEL, REMBRANDT, and GILL datasets. Differentially expressed genes were analyzed and NEK2 was picked as a candidate gene for subsequent validation. Human tissue samples and corresponding data were collected from our center and detected by immunohistochemistry analysis. Molecular biological assays and in vivo xenograft transplantation were performed to confirm the bioinformatic findings. High-throughput RNA sequencing, followed by KEGG analysis, GSEA analysis and GO analysis were conducted to identify potential signaling pathways related to NEK2 expression. Subsequent mechanism assays were used to verify the relationship between NEK2 and NF-κB signaling. Overall, we identified that NEK2 is significantly upregulated in GBM and the higher expression of NEK2 exhibited a poorer prognosis. Functionally, NEK2 knockdown attenuated cell proliferation, migration, invasion, and tumorigenesis of GBM while NEK2 overexpression promoted the GBM progression. Furthermore, High-throughput RNA sequencing and bioinformatics analysis indicated that NEK2 was positively related to the NF-κB signaling pathway in GBM. Mechanically, NEK2 activated the noncanonical NF-κB signaling pathway by phosphorylating NIK and increasing the activity and stability of NIK. In conclusion, NEK2 promoted the progression of GBM through activation of noncanonical NF-κB signaling, indicating that NEK2- NF-κB axis could be a potential drug target for GBM.

Dataset Information

Vitamin D regulates contractile profile in human uterine myometrial cells via NF-?B pathway.

Publications

Vitamin D regulates contractile profile in human uterine myometrial cells via NF-κB pathway.

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