Biology subjects

Tsuruta, D.

Publications and source records attributed to Tsuruta, D..

2 recordsLinked to original sources

bioRxiv2022

Disorganization of basement membrane zone architecture causes impaired melanocyte inhabitation in vitiligo

Vitiligo, a chronic autoimmune skin disorder characterized by selective epidermal melanocyte loss, lacks a well-defined mechanism for this phenomenon. Our study offers compelling insights into vitiligo pathogenesis by revealing disruptions in the basement membrane zone (BMZ) architecture. We observed branched, fragmented, and multilayered lamina densa, accompanied by elevated dermal fibroblast numbers and notable matrix metalloproteinase 2 (MMP2) overexpression. Vitiliginous skin extracts exhibited significant active MMP2 upregulation. To establish a direct link, we intradermally injected MMP2-overexpressing fibroblasts into K14-SCF transgenic mice, resulting in vitiligo-like skin and melanocyte loss, effectively reversed by coadministering MMP2 inhibitors. These groundbreaking findings highlight the pivotal role of disorganized BMZ in vitiligo, proposing MMP2 overexpression in dermal fibroblasts as a potential key contributor. Enhancing our understanding of vitiligos mechanisms, this research opens avenues for innovative therapeutic strategies against this challenging autoimmune skin disorder. TeaserDisrupted skin architecture and MMP2 in dermal fibroblasts hold the key to a potential breakthrough against this puzzling autoimmune disease vitiligo.

pathology↗

bioRxiv2021

OTUD1 deubiquitylase regulates NF-κB- and KEAP1-mediated inflammatory responses and reactive oxygen species-associated cell death pathways

Deubiquitylating enzymes (DUBs) regulate numerous cellular functions by removing ubiquitin modifications. We examined the effects of 88 human DUBs on linear ubiquitin chain assembly complex (LUBAC)-induced NF-{kappa}B activation, and identified OTUD1 as a potent suppressor. OTUD1 regulates the canonical NF-{kappa}B pathway by hydrolysing K63-linked ubiquitin chains from NF-{kappa}B signalling factors, including LUBAC. OTUD1 negatively regulates the canonical NF-{kappa}B activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway. The N-terminal intrinsically disordered region of OTUD1, which contains an EGTE motif, is indispensable for KEAP1-binding and NF-{kappa}B suppression. OTUD1 is involved in the KEAP1-mediated antioxidant response and reactive oxygen species (ROS)-induced cell death, oxeiptosis. In Otud1-/--mice, inflammation, oxidative damage, and cell death were enhanced in inflammatory bowel disease, acute hepatitis, and sepsis models. Thus, OTUD1 is a crucial regulator for the inflammatory, innate immune, and oxidative stress responses and ROS-associated cell death pathways.

cell biology↗