Keio University · Neuroscience
Professor Masato Fujioka's research lab focuses on the molecular and cellular mechanisms underlying inner ear inflammation, immune responses, and degenerative hearing loss. The lab investigates the role of resident immune cells—particularly macrophages—in cochlear pathologies induced by noise, mitochondrial dysfunction, and genetic disorders such as Wolfram syndrome. Using advanced models including transgenic mice and nonhuman primates, the lab explores the dynamics of cell death, regeneration, and the inflammatory microenvironment in the cochlear lateral wall, especially in spiral ligament fibrocytes. Their work bridges immunology, otology, and regenerative biology to uncover therapeutic targets for sensorineural hearing loss.
Figures are computed from collected data and may differ slightly.
Recent studies have showed that inflammatory responses occur in inner ear under various damaging conditions including noise-overstimulation. We evaluated the time-dependent expression of proinflammatory cytokines in noise-exposed rat cochlea. Among several detected cytokines, real-time RT-PCR showed that interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) were significantly induced 3 hr after noise exposure, and quickly downregulated to the basal level. Tumor necrosis factor-alpha (TNF-alpha)
The inner ear was previously assumed to be an "immune-privileged" organ due to the existence of its tight junction-based blood-labyrinth barrier. However, studies performed during the past decade revealed that the mesenchymal region of the cochlea, including its lateral wall, is a common site of inflammation. Neutrophils do not enter this region, which is consistent with the old dogma; however, bone marrow-derived resident macrophages are always present in the spiral ligament of the lateral wall
Wolfram syndrome is an autosomal recessive disorder of the neuroendocrine system, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness) syndrome, and considered an endoplasmic reticulum disease. Patients show mutations in WFS1, which encodes the 890 amino acid protein wolframin. Although Wfs1 knockout mice develop diabetes, their hearing level is completely normal. In this study, we examined the expression of wolframin in the cochlea of a nonhuman primate common ma
Cochlear lateral wall has recently been reported as a common site of inflammation, yet precise molecular mechanisms of the inflammatory responses remain elucidated. The present study examined the inflammatory responses in the lateral wall following acute mitochondrial dysfunction induced by a mitochondrial toxin, 3-nitropropionic acid (3-NP). Reverse-transcription (RT)-PCR revealed increases in the expression of the proinflammatory cytokines interleukin (IL)-1β and IL-6. Immunohistochemistry sho
Most degenerative diseases begin with a gradual loss of specific cell types before reaching a threshold for symptomatic onset. However, the endogenous regenerative capacities of different tissues are difficult to study, because of the limitations of models for early stages of cell loss. Therefore, we generated a transgenic mouse line (Mos-iCsp3) in which a lox-mismatched Cre/lox cassette can be activated to produce a drug-regulated dimerizable caspase-3. Tissue-restricted Cre expression yielded
Cochlear spiral ligament fibrocytes (SLFs) play essential roles in the physiology of hearing including ion recycling and the generation of endocochlear potential. In adult animals, SLFs can repopulate after damages, yet little is known about the characteristics of proliferating cells that support SLFs' self-renewal. Here we report in detail about the characteristics of cycling cells in the spiral ligament (SL). Fifteen P6 mice and six noise-exposed P28 mice were injected with 5-bromo-2'-deoxyuri
JMA-IIA00361; Pre-results.
Recent studies have indicated that direct administration of viral vectors or small compounds to the inner ear may aid in the treatment of Sensorineural hearing loss (SNHL). However, due to species differences between humans and rodents, translating experimental results into clinical applications remains challenging. The common marmoset (<i>Callithrix jacchus</i>), a New World monkey, is considered a pre-clinical animal model. In the present study, we describe morphometric data acquired from the
Open papers in the app to read, cite, and organize with AI.
