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Honda, C.

Publications and source records attributed to Honda, C..

2 recordsLinked to original sources

Effects of Arachis hypogaea extract on TRPV4 activation and epidermal barrier function

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel and its activating stimuli include anandamide, bisandrographolide, citric acid, arachidonic acid metabolic products by epoxygenases, hypo-osmotic cell swelling, and warm temperature. TRPV4 is involved in Ca2+-dependent signal transduction in several tissues. Since the activation of TRPV4 facilitates adherens junction formation in the skin epithelium, compounds that activate TRPV4 are expected to maintain or improve the barrier function of epidermal cells. In this study, we found that the extract of Arachis hypogaea (A. hypogaea) activate human TRPV4 (hTRPV4). In the Ca2+-imaging experiment, the application of A. hypogaea extract exhibited an increase in intracellular Ca2+ concentration ([Ca2+]i) in HEK293T cells expressing hTRPV4. The [Ca2+]i increases by application of A. hypogaea extract were not observed in HEK293T cells expressing hTRPV1, mouse TRPV2, hTRPV3, hTRPM8, or hTRPA1. We then examined the physicochemical properties of the components responsible for TRPV4 activation. Ethanol extracts of A. hypogaea caused an increase in [Ca2+]i in hTRPV4-expressing HEK293JN cells, whereas water, chloroform, and hexane extracts showed no activity. Moreover, the application of A. hypogaea extract enhanced transepithelial electrical resistance in the keratinocyte monolayer. These results suggest that A. hypogaea extract may contribute to the maintenance and improvement of the epidermal barrier function.

pharmacology and toxicology↗

Cancer-associated Fibroblast Spatial Heterogeneity and EMILIN1 Expression in Cancer Stroma Modulate TGF-beta Activity and CD8+ T-Cell Infiltration in Breast Cancer

The tumor microenvironment (TME) and its multifaceted interactions with cancer cells are major targets for cancer treatment. Single-cell technologies have brought major insights into the TME, but the resulting complexity frequently precludes conclusions on function. Therefore, we combined single-cell RNA sequencing and spatial transcriptomic data to explore the relationship between different cancer-associated fibroblast (CAF) populations and immune cell exclusion in breast tumors. Our data show for the first time the degree of spatial organization of different CAF populations in breast cancer. We found that IL-iCAFs, Detox-iCAFs, and IFN{gamma}-iCAFs tended to cluster together, while Wound-myCAFs, TGF{beta}-myCAFs, and ECM-myCAFs formed another group that overlapped with elevated TGF-{beta} signaling. Differential gene expression analysis of areas with CD8+ T-cell infiltration/exclusion within the TGF-{beta} signaling-rich zones identified elastin microfibrillar interface protein 1 (EMILIN1) as a top modulated gene. EMILIN1, a TGF-{beta} inhibitor, was upregulated in IFN{gamma}-iCAFs directly modulating TGF{beta} immunosuppressive function. Histological analysis of 74 breast cancer samples confirmed that high EMILIN-1 expression in the tumor margins was related to high CD8+ T-cell infiltration, consistent with our spatial gene expression analysis. High EMILIN-1 expression was also associated with better prognosis of patients with breast cancer, underscoring its functional significance for the recruitment of cytotoxic T cells into the tumor area. In conclusion, our data show that correlating TGF-{beta} signaling to a CAF subpopulation is not enough because proteins with TGF-{beta}-modulating activity originating from other CAF subpopulations can alter its activity. Therefore, therapeutic targeting should remain focused on biological processes rather than on specific CAF subtypes.

cancer biology↗