Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
Volume 43, Issue 3
Displaying 1-4 of 4 articles from this issue
Review
  • Toshihiko IWANAGA, Hiromi TAKAHASHI-IWANAGA
    Article type: research-article
    2022 Volume 43 Issue 3 Pages 59-72
    Published: June 19, 2022
    Released on J-STAGE: June 20, 2022
    JOURNAL FREE ACCESS

    Gut epithelial cells are characterized by rapid, constant cell renewal. The disposal of aging epithelial cells around the villus tips of the small intestine occurs so regularly that it has been regarded as a consequence of well-controlled cell death, designated as apoptosis. However, the notion of live cell extrusion in the intestine has been intensively built among researchers, and the disposal processes of effete epithelial cells display species and regional differences. Chemical mediators and mechanical forces rising from surrounding cells contribute to the regulated cell replacement. Cytotoxic intraepithelial lymphocytes and lamina propria macrophages play a leading role in the selection of disposal cells and their extrusion to maintain fully the epithelial homeostasis in tandem with the dynamic reconstruction of junctional devices. Lymphocyte-mediated cell killing is predominant in the mouse and rat, while the disposal of epithelial cells in the guinea pig, monkey, and human is characterized by active phagocytosis by subepithelially gathering macrophages. The fenestrated basement membrane formed by immune cells supports their involvement and explains species differences in the disposal of epithelial cells. Via these fenestrations, macrophages and dendritic cells can engulf apoptotic epithelial cells and debris and convey substantial information to regional lymph nodes. In this review, we attempt to focus on morphological aspects concerning the apoptosis and disposal process of effete epithelial cells; in vitro or ex vivo analyses using cultured monolayer has become predominant in recent studies concerning the exfoliation of apoptotic enterocytes. Furthermore, we give attention to their species differences, which is controversial but crucial to our understanding.

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Full Papers
  • Yumi AIZAWA, Masaru MORI, Tsukasa SUZUKI, Akihiro SAITO, Hirofumi INOU ...
    Article type: research-article
    2022 Volume 43 Issue 3 Pages 73-80
    Published: June 19, 2022
    Released on J-STAGE: June 20, 2022
    JOURNAL FREE ACCESS
    Supplementary material

    Arginine methylation is a common post-translational modification which functions as an epigenetic regulator of transcription and plays a key role in various cell signaling pathways. The methylation of arginine residues is catalyzed by protein arginine methyltransferase (PRMT). However, the expression pattern and underlying mechanism of PRMTs and protein methylation profile in lipopolysaccharide (LPS)-induced innate immune responses are poorly understood. Using a shotgun proteomic approach, we found that LPS stimulation increased arginine and proline metabolism and responses to inflammation and bacterial infections. In comparison, cysteine and methionine metabolism, the pentose phosphate pathway, purine metabolism, and protein methylation factors were also decreased in LPS stimulated murine macrophage cell lines. We revealed that LPS stimulation downregulated PRMT1, PRMT5, and protein arginine methylation profiles in RAW264.7 cells using western blot analysis. Additionally, this phenomenon occurred in parallel with nitric oxide accumulation in LPS-induced macrophages. Using inflammation models, we demonstrate for the first time that LPS stimulation decreases PRMTs, leading to the decreasing of arginine methylation in macrophages.

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  • Jing QIN, Wu-shuang HUANG, Hao-ran DU, Chun-qing ZHANG, Peng XIE, Han ...
    Article type: research-article
    2022 Volume 43 Issue 3 Pages 81-89
    Published: June 19, 2022
    Released on J-STAGE: June 20, 2022
    JOURNAL FREE ACCESS

    The claustrum has been hypothesized to participate in high-order brain functions, but experimental studies to demonstrate these functions are currently lacking. Neural activity recording of the claustrum in freely-behaving animals allows for correlating claustral activities with specific behaviors. However, previously utilized methods for studying the claustrum make it difficult to monitor neural activity patterns of freely-behaving animals in real time. Here we applied fiber photometry to monitor Ca2+ activity in the claustrum of freely-behaving mice. Using this method, we were able to achieve Ca2+ activity recording in both anesthetized and freely-behaving mice. We found that the dynamics of Ca2+ activity depended on anesthesia levels. As compared to the use of genetically encoded Ca2+ indicators that requires a few weeks of virus-dependent expression, we used a synthetic fluorescent Ca2+-sensitive dye, Oregon green 488 BAPTA-1, that allows for rapidly screening neural activity of interest within a few hours that relates to certain behaviors. In this way, we found the correlation between Ca2+ activity and specific behaviors, such as approaching an object. Our work offers an effective method for recording neural activity in the claustrum and thus for rapidly screening any behavioral relevance of the claustrum in freely-behaving mice.

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  • Eriko ISOGAI, Kazuhiro OKUMURA, Megumi SAITO, Yurika TOKUNAGA, Yuichi ...
    Article type: research-article
    2022 Volume 43 Issue 3 Pages 91-97
    Published: June 19, 2022
    Released on J-STAGE: June 20, 2022
    JOURNAL FREE ACCESS

    Meis1 (myeloid ecotropic insertion site 1) is known to be related to embryonic development and cancer. In this study, to analyze the function of Meis1 in neural stem cells, we crossed Meis1fl/fl (Meis1 floxed) mice with Nestin-Cre mice. The results showed that Meis1-conditional knockout mice showed cerebral cortex malformation. The mice had a significantly thinner cortex than wildtype mice. At E14.5, BrdU incorporation and Pax6-positive radial glial cells were significantly decreased in the cerebral cortex of Meis1 knockout embryos as compared with wild-type embryos, whereas Tbr2-positive intermediate progenitors and NeuN-positive differentiated neurons were not. Cell death detected by immunostaining with cleaved caspase3 antibody showed no difference in the cortex between knockout and wild-type embryos. Furthermore, knockout of Meis1 in embryo by in utero electroporation showed that cellular migration was disturbed during cortical development. Therefore, Meis1 could play important roles during cortical development through the regulation of cell proliferation and migration in the embryonic cerebral cortex.

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