Biology subjects

Fukuda, J.

Publications and source records attributed to Fukuda, J..

3 recordsLinked to original sources

bioRxiv2026

Co-targeting an AMPK--MAPK axis reprograms CAFs and suppresses PDAC

Pancreatic ductal adenocarcinoma (PDAC) is a fatal cancer characterized by limited therapeutic options and a highly treatment-resistant tumor microenvironment. Beyond tumor-intrinsic genetic alterations, growing evidence indicates that host-microbiome interactions influence cancer progression through microbial metabolites. However, how microbiome-derived metabolites influence oncogenic signaling in PDAC remains unclear. Here, integrated profiling revealed a consistent reduction of the microbial metabolite acetic acid in fecal samples from treatment-naive patients with PDAC and in a genetically defined Drosophila model recapitulating key PDAC driver alterations. Acetic acid activates AMP-activated protein kinase, and pharmacological activation of this pathway together with inhibition of mitogen-activated protein kinase signaling suppressed tumor growth in fly and mouse models. Combined pathway targeting restored AMPK activity and suppressed cancer-associated fibroblast activation. These findings identify a microbiome-associated metabolic vulnerability in PDAC and suggest that coordinated targeting of metabolic and oncogenic signaling may restrain tumor progression and improve therapeutic strategies.

cancer biology↗

bioRxiv2025

Hair Dermal papilla maintain its hair inducing characteristics via autocrine exosomal miR-23a-3p

Human dermal papilla cells (hDPCs) are specialized mesenchymal cells that regulate hair follicle development and drive the hair cycle. However, when cultured in vitro, hDPCs progressively lose their hair-inductive capacity. This decline may be closely associated with the absence of the native microenvironmental niche, which plays a critical role in maintaining hDPC identity and function in vivo. In addition to extrinsic cues, autocrine signaling within the dermal papilla itself may serve as a key mechanism for sustaining its regenerative potential. In this study, we present a novel growth model that enables real-time tracking of hDPC functional recovery, with particular attention to autocrine signaling and niche reprogramming. Our results reveal that intrinsic feedback loops are essential for maintaining hDPC function during the anagen phase. By elucidating the dynamic interplay between hDPC expansion and hair-inductive capacity, this work advances our understanding of hair follicle biology and highlights new avenues for developing regenerative therapies for hair loss.

bioengineering↗

bioRxiv2022

Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction

During embryonic development, reciprocal interactions between epidermal and mesenchymal layers trigger hair follicle morphogenesis. This study revealed that microenvironmental reprogramming via control over these interactions enabled hair follicle induction in vitro. A key approach is to modulate spatial distributions of epithelial and mesenchymal cells in their spontaneous organization. The de novo hair follicles with typical morphological features emerged in aggregates of the two cell types, termed hair follicloids, and hair shafts sprouted with near 100% efficiency in vitro. The hair shaft length reached [~]3 mm in culture. Typical trichogenic signaling pathways were upregulated in hair follicloids. Owing to replication of hair follicle morphogenesis in vitro, production and transportation of melanosomes were also monitored in the hair bulb region. This in vitro hair follicle model might be valuable for better understanding hair follicle induction, for evaluating hair growth as well as the inhibition of hair growth by drugs, and modeling gray hairs in a well-defined environment. TeaserIn tissue morphogenesis, different types of cells harmonize in a pre-programmed manner using messenger systems such as epithelial-mesenchymal interactions. Organoids are a promising tool to elucidate such mechanisms on a molecular level. This work describes a strategy for reprograming three-dimensional microenvironments to trigger the initiation of in vitro regeneration of hair follicle organoids. Hair follicle organoids generated fully matured hair follicles, enabling the monitoring of hair follicle morphogenesis in vitro and determination of signaling pathways involved in early hair follicle morphogenesis. The principles uncovered herein may be relevant to other organ systems and will contribute to our understanding of developmental phenomena in physiological and pathological processes, eventually opening up new research avenues for the development of new treatment strategies.

bioengineering↗