Biology subjects

Hattori, S.

Publications and source records attributed to Hattori, S..

5 recordsLinked to original sources

bioRxiv2021

Bi-phasic effect of gelatin in myogenesis and skeletal muscle regeneration

Skeletal muscle regeneration requires extracellular matrix (ECM) remodeling including an acute and transient breakdown of collagen that produces gelatin. However, the physiological function of such a remodeling process on muscle tissue repair is unclear. Here we elaborate on a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by hormetic effects of reactive oxygen species (ROS). Low-dose gelatin stimulates ROS production from NADPH oxidase 2 (NOX2) and simultaneously upregulates antioxidant system for cellular defense, reminiscent of the adaptive compensatory process during mild stress. This response triggers the release of myokine IL-6 which stimulates myogenesis and facilitates muscle regeneration. By contrast, high-dose gelatin stimulates ROS overproduction from NOX2 and mitochondrial chain complex, and ROS accumulation by suppressing antioxidant system, triggering release of TNF, which inhibits myogenesis and regeneration. Our findings reveal gelatin-ROS-IL-6/TNF signaling cascades underlying a hormetic response of myogenic cells to gelatin.

physiology↗

bioRxiv2021

Humanized substitutions of Vmat1 in mice induce changes in amygdala-dependent behaviors associated with the evolution of anxiety in humans

The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmission, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse Vmat1 via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological and molecular levels. Behavioral tests revealed reduced anxiety-related traits of Vmat1Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified amygdala-specific changes in the expression of genes involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors.

evolutionary biology↗

bioRxiv2021

Preservation of collagen in the soft tissues of frozen mammoths

We investigated the characteristics of extracellular matrix (ECM) in the soft tissue of two frozen baby woolly mammoths (Mammuthus primigenius) that died and were buried in Siberian permafrost approximately 40,000 years ago. Morphological and biochemical analyses of mammoth lung and liver demonstrated that those soft tissues were preserved at the gross anatomical and histological levels. The ultrastructure of ECM components, namely a fibrillar structure with a collagen-characteristic pattern of cross-striation, was clearly visible with transmission and scanning electron microscopy. Type I and type IV collagens were detected by immunohistochemical observation. Quantitative amino acid analysis of liver and lung tissues of the baby mammoths indicated that collagenous protein is selectively preserved in these tissues as a main protein. Type I and type III collagens were detected as major components by means of liquid chromatography-mass spectrometry analysis after digestion with trypsin. These results indicate that the triple helical collagen molecule, which is resistant to proteinase digestion, has been preserved in the soft tissues of these frozen mammoths for 40,000 years.

paleontology↗

bioRxiv2020

Adhesion to type I collagen fibrous gels induces E- to N- cadherin switching without other EMT-related phenotypes in lung carcinoma cell A549

In culture system, environmental factors, such as increasing exogenous growth factors and adhesion to type I collagen (Col-I) induce epithelial-to-mesenchymal transition (EMT) in cells. Col-I molecules maintain a non-fibril form under acidic conditions, and they reassemble into fibrils under physiological conditions. Col-I fibrils often assemble to form three-dimensional gels. The gels and non-gel-form of Col-I can be utilized as culture substrates and different gel-forming state often elicit different cell behaviors. However, gel-form dependent effects on cell behaviors, including EMT induction, remain unclear. EMT induction in lung cancer cell line A549 has been reported via adhesion to Col-I but the effects of gel form dependency are unelucidated. This study investigated the changes in EMT-related behaviors in A549 cells cultured on Col-I gels. We examined cell morphology, proliferation, single-cell migration and expression of EMT-related features in A549 cells cultured on gels or non-gel form of Col-I and non-treated dish with or without transforming growth factor (TGF)-{beta}1. On Col-I gels, some cells kept cell-cell contacts and formed clusters, others maintained single-cell form. In cell-cell contact regions, E-cadherin expression was downregulated, whereas that of N-cadherin was upregulated. Vimentin and integrins 2 and {beta}1 expression were not increased. In TGF-{beta}1-treated A549 cells, cadherin switched from E- to N-cadherin. Their morphology changed to a mesenchymal form and cells scattered with no cluster formation. Vimentin, integrins 2 and {beta}1 expression were upregulated. Thus, we concluded that culture on Col-I fibrous gels induced E- to N-cadherin switching without other EMT-related phenotypes in A549 cells.

cell biology↗

bioRxiv2019

Suppression of DSB Formation by Polβ in Active DNA Demethylation is Required for Postnatal Hippocampal Development

Genome stability is essential for brain development and function. However, the contribution of DNA repair to genome stability in neurons remains elusive. Here, we demonstrate that the base excision repair protein Pol{beta} is involved in hippocampal neuronal differentiation via a TET-mediated active DNA demethylation during early postnatal stages. Pol{beta} deficiency induced extensive DNA double-strand breaks (DSBs) in hippocampal neurons, and a lesser extent in cortical neurons, during a period in which decreased levels of 5-methylcytosine were observed in genomic DNA. Inhibition of the hydroxylation of 5-methylcytosine by microRNAs miR29a/b-1 expression diminished DSB formation. Conversely, its induction by TET1 overexpression increased DSBs. The damaged hippocampal neurons exhibited aberrant neuronal gene expression profiles and dendrite formation. Behavioral analyses revealed impaired spatial learning and memory in adulthood. Thus, Pol{beta} maintains genome stability in the active DNA demethylation that occurs during postnatal neuronal development, thereby contributing to differentiation and subsequent behavior.

neuroscience↗