Biology subjects

Buscail, E.

Publications and source records attributed to Buscail, E..

3 recordsLinked to original sources

bioRxiv2025

Goblet cells mechanically breach the epithelial barrier in gut homeostasis

The intestinal epithelium has to maintain a tight barrier against the harsh luminal environment. Absorptive enterocytes have a polygonal and columnar shape, while mucus-producing goblet cells exhibit a round apical cell shape and a bulky body, raising the question of how epithelial integrity is maintained around these cells. Here, we show that goblet cells induce tight junction fractures between neighboring enterocytes under homeostatic conditions in vivo, which are exacerbated during goblet cell hypertrophy, increasing gut permeability. We demonstrate that these fractures arise from a two-component mechanical interaction: goblet cells push and deform adjacent enterocytes, which rupture depending on tissue rheology controlled by myosin II. These findings reveal that the mechanical interplay between goblet cells and neighboring enterocytes is critical for maintaining intestinal epithelial barrier integrity.

cell biology↗

bioRxiv2024

Regenerative potential of human enteric glia in a preclinical model of acute brain injury

BackgroundAcute brain injury is characterized by extensive tissue damage, resulting in neuronal loss and functional deficits in patients. The capacity of nerve tissue to self-regenerate is insufficient to repair damaged tissue, thus therapies based on exogenous cells are urgently needed. Human enteric glia (EG) have interesting intrinsic properties that make them a valuable candidate for regenerative medicine. In this long-term study, we investigated whether human EG treatment induces tissue repair and improves functional recovery in a rat model of brain injury. MethodsAcute brain injury was induced by malonate injection in the motor cortex of female rats, causing extensive tissue damage and long-lasting sensorimotor deficits. Human EG were isolated from gut tissue, expanded and administered intranasally in awake immunocompetent rats. To determine the long-term safety and efficacy of human EG treatment, longitudinal evaluation of sensorimotor function, post-mortem tissue regeneration and the fate of human EG were assessed thirty-six weeks after intranasal administration. ResultsTransplanted human EG satisfied the safety criteria, non-immunogenic and non-tumorigenic, required for cell therapy; they were well tolerated in immunocompetent rats, and induced sensorimotor improvement. Importantly, thirty-six weeks post-treatment, intranasally delivered human EG were detected in the rat brain, mainly in the injured motor cortex. This indicated that transplanted human EG migrated and successfully engrafted and integrated with the host tissue. Additionally, human EG induced tissue regeneration by enhancing endogenous angiogenesis and neurogenesis. Notably, thirty-six weeks after administration, human EG generated mature neurons that were enveloped by oligodendrocytes and formed synaptic connections with the host tissue. ConclusionsTransplanted human EG induced tissue repair and showed regenerative potential after brain injury. This is the first study demonstrating the feasibility, safety and efficacy of intranasal administration of human EG for treatment of brain injury.

neuroscience↗

bioRxiv2024

TRPV4 stimulates colonic afferents through mucosal release of ATP and glutamate

Background and PurposeAbdominal pain is a leading cause of morbidity for people living with gastrointestinal disease. While the vanilloid transient receptor potential 4 (TRPV4) ion channel has been implicated in the pathogenesis of abdominal pain, the relative paucity of TRPV4 expression in colon-projecting sensory neurons suggests that non-neuronal cells may also contribute to TRPV4-mediated nociceptor stimulation. Experimental ApproachChanges in murine colonic afferent activity were examined using ex vivo electrophysiology in tissues with the gut mucosa present or removed. ATP and glutamate release were measured by bioluminescence assay from human colon organoid cultures and mouse colon. Dorsal root ganglion sensory neuron activity was evaluated by Ca2+ imaging when cultured alone or co-cultured with colonic mucosal cells. Key ResultsThe TRPV4 agonist GSK1016790A elicited a robust increase in murine colonic afferent activity, which was abolished by removal of the gut mucosa. GSK1016790A promoted ATP and glutamate release from human colon organoid cultures and mouse colon. Inhibition of ATP degradation in mouse colon enhanced the afferent response to GSK1016790A. Pre-treatment with purinoreceptor or glutamate receptor antagonists attenuated and abolished the response to GSK1016790A when given alone or in combination, respectively. Sensory neurons co-cultured with colonic mucosal cells produced a marked increase in intracellular Ca2+ to GSK1016790A compared to neurons cultured alone. Conclusions and ImplicationsOur data indicate that mucosal release of ATP and glutamate is responsible for the stimulation of colonic afferents following TRPV4 activation. These findings highlight an opportunity to target the gut mucosa for the development of new visceral analgesics. Bullet Point SummaryWhat is already known? O_LIActivation of TRPV4 causes visceral hypersensitivity via the stimulation of colonic afferents. C_LI What does this study add? O_LITRPV4-mediated colonic afferent activation is dependent on mucosal release of ATP and glutamate. C_LI What is the clinical significance? O_LIMucosal TRPV4-mediated colonic afferent activation provides a gut restricted target for treating abdominal pain. C_LI

pharmacology and toxicology↗