Biology subjects

Minami, Y.

Publications and source records attributed to Minami, Y..

4 recordsLinked to original sources

bioRxiv2023

Wnt5a-Ror2 signaling activates p62-Nrf2 axis in reactive astrocytes after brain injury

In the brains under pathological conditions, astrocytes become reactive astrocytes that exhibit various context-dependent functions through the regulation of specific signaling pathways and transcriptional mechanisms in response to environmental changes. Reactive astrocytes induced in injured brains begin proliferating and play a role in promoting protection and repair of damaged tissues, but the relationship between the proliferative characteristics and tissue-protective and repair functions of reactive astrocytes remains unclear. Here, we show that growth factor signaling elicited by bFGF and HB-EGF, whose expression is up-regulated in the injured brains, acts synergistically with inflammatory cytokine signaling in astrocytes, thereby markedly up-regulating gene expression of the Ror-family protein Ror2, a receptor for Wnt5a. Activation of Wnt5a-Ror2 signaling in astrocytes results in intracellular accumulation of phosphorylated p62, thereby activating antioxidative transcription factor Nrf2. Finally, we provide evidence demonstrating that forced activation of Wnt5a-Ror2-p62-Nrf2 signaling axis in astrocytes reduces cellular damage caused by hemin, a degradation product of hemoglobin, and promotes repair of the damaged blood brain barrier after brain hemorrhage.

molecular biology↗

bioRxiv2022

Liver lipophagy ameliorates nonalcoholic steatohepatitis through lysosomal lipid exocytosis

Nonalcoholic steatohepatitis (NASH) is a progressive disorder with aberrant lipid accumulation and subsequent inflammatory and profibrotic response. Therapeutic efforts at lipid reduction via increasing cytoplasmic lipolysis unfortunately worsens hepatitis due to toxicity of liberated fatty acid. An alternative approach could be lipid reduction through autophagic disposal, i.e., lipophagy. We engineered a synthetic adaptor protein to induce lipophagy, combining a lipid droplet-targeting signal with optimized LC3-interacting domain. Activating hepatocyte lipophagy in vivo strongly mitigated both steatosis and hepatitis in a diet-induced mouse NASH model. Mechanistically, activated lipophagy promoted the excretion of lipid from hepatocytes via lysosomal exocytosis, thereby suppressing harmful intracellular accumulation of nonesterified fatty acid. A high-content compound screen identified alpelisib and digoxin, clinically-approved compounds, as effective activators of lipophagy. Administration of alpelisib or digoxin in vivo strongly inhibited the transition to steatohepatitis. These data thus identify lipophagy as a promising therapeutic approach to prevent NASH progression.

cell biology↗

bioRxiv2019

Capsicum cultivated under adverse conditions in Southern Japan produces higher concentrations of antioxidants and pungent components

Growing crops in sabulous soils is often challenging due to their limited oligotrophy and weak water retention. However, some plants adapt to these adverse growth conditions, and in some cases, favorable properties are imparted to the fruit. This study investigated the influence of the cultivation environment on Capsicum by assessing the levels and functions of both pungent components and antioxidants when cultivated in sandy soils in Southern Japan; these parameters were then compared to those in traditional tropical-origin Capsicum. In seven varieties of Capsicum, the distribution of capsaicin and dihydrocapsaicin differed between the pericarp and seeds within the placenta. The leaves and fruits of Habanero orange and Tabasco, which are the most suitable for cultivation in sandy soil, were collected during the cultivation period and analyzed in terms of their size, color, and pungent component composition. Pungent components were detected in fruits only, and not in leaf or flower samples. In particular, we found that pungent components were generally present within the seeds and placenta. Antioxidant activity and nitric oxide production within human vascular endothelial cells were also evaluated to compare the differences in their functionality. Satsuma-Habanero orange cultivated under adverse conditions possessed the highest antioxidant activity. Furthermore, Satsuma-Capsicum cultivated under adverse conditions exhibited higher levels of antioxidants than traditional tropical-origin peppers, and induced similar levels of nitric oxide production in the vascular endothelial cells. We concluded that Capsicum cultivated in harsh environments produced beneficial effects such as higher levels of antioxidants and capsaicinoids in seeds and placenta. Moreover, the fruits from these plants could be harvested for a significantly longer period and took longer to spoil than traditional Capsicum; thus, they show merit as a viable commercial crop in Japan.

plant biology↗

bioRxiv2018

Synchronized mesenchymal cell polarization and differentiation shape the formation of the murine trachea and esophagus

Tube morphogenesis is essential for internal-organ development, yet the mechanisms regulating tube shape remain unknown. Here we show that different mechanisms regulate the length and diameter of the murine trachea. First, we found that trachea development progresses via elongation and expansion processes. In the first stage, synchronized radial polarization of smooth muscle (SM) progenitor cells with inward Golgi-apparatus displacement regulates tube elongation, controlled by mesenchymal Wnt5a-Ror2 signaling. This radial polarization directs SM progenitor cell migration toward the epithelium, and the resulting subepithelial morphogenesis supports tube elongation to the anteroposterior axis. This radial polarization also regulates esophageal elongation. Subsequently, cartilage development helps expand the tube diameter, which drives epithelial cell reshaping to determine the optimal lumen shape for efficient respiration. These findings suggest a strategy in which straight-organ tubulogenesis is driven by subepithelial cell polarization and ring cartilage development.

developmental biology↗