Biology subjects

Uehara, Y.

Publications and source records attributed to Uehara, Y..

4 recordsLinked to original sources

bioRxiv2023

Pulmonary osteoclast-like cells in silica induced pulmonary fibrosis

The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored the mechanisms of silica-induced pulmonary fibrosis in a mouse model using multiple modalities including wholelung single-nucleus RNA sequencing. These analyses revealed that in addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor-{kappa}B ligand (RANKL) in pulmonary lymphocytes and alveolar type II cells. Furthermore, anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated silica-induced pulmonary fibrosis. We conclude that silica induces osteoclast-like differentiation of distinct recruited and tissue resident monocyte populations, leading to progressive lung injury, likely due to sustained elaboration of bone resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis. One Sentence SummarySilica induces the alveolar epithelium to reprogram recruited and resident pulmonary myeloid cells to become osteoclasts that contribute to pulmonary fibrosis.

pathology↗

bioRxiv2021

Novel insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a PAM lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes suggested a role for osteoclast-like cells in the defense against microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activity in a receptor activator of nuclear factor-{kappa}B ligand (RANKL) and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.

molecular biology↗

bioRxiv2021

Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

Non-invasive acquisition of mRNA data from the skin would be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable human mRNAs exist in SSLs, where sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNAs, and our results revealed that SSL-RNAs predominantly contained mRNAs derived from sebaceous glands, epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal differentiation-related genes, consistent with the results of previous reports. Further, we found that lipid synthesis-related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is promising to understand the pathophysiology of skin diseases.

molecular biology↗

bioRxiv2020

The effects of temporal continuities of grasslands on the diversity and species composition of plants

Semi-natural grasslands are ecosystems rich in biodiversity. However, their decline has been reported worldwide, and identification of grasslands with high conservation priority is urgently required. Recently, an increasing number of studies have reported that past vegetation history affects current biological communities. To evaluate whether the temporal continuity of grasslands promotes biodiversity, and thus can be an indicator of conservation priority, we studied vascular plant communities in old (160- 1000s years) and new (52-70 years after deforestation) grasslands, as well as in forests, of Sugadaira Highland in central Japan. The number of plant species was highest in old grasslands, followed by new grasslands and forests. This pattern was much clearer in the number of grassland-dependent native and grassland-dependent endangered species, indicating the role of old grasslands as refugia for those species. The species composition differed between old and new grasslands. New grasslands had species compositions in between those of old grasslands and forests, suggesting that the plant community in new grasslands retains the influence of past forestation for more than 52 years after deforestation. Eleven indicator species were detected in old grasslands, but none in new grasslands, suggesting the uniqueness of the plant community in old grasslands. We conclude that the temporal continuity of grasslands increases plant diversity and can be an indicator of grasslands with high conservation priority.

ecology↗