Biology subjects

Muramatsu, R.

Publications and source records attributed to Muramatsu, R..

2 recordsLinked to original sources

bioRxiv2024

CSF pressure in fetal mice in utero: External factors pressurize the intraventricular space

Previous experiments inducing leakage of embryonic cerebrospinal fluid (CSF) suggest the necessity of intraventricular CSF pressure (PCSF) for brain morphogenesis. Nevertheless, how embryonic PCSF occurs is unclear, especially in utero. Using a Landis water manometer, we measured PCSF in fetal mice isolated from the amniotic cavity (PCSF-ISO). At embryonic day (E) 13, PCSF-ISO was 82.7 Pa. Intraventricular injections of [≥]2 l of saline elevated PCSF-ISO by [~]30%. Intraventricularly injecting inhibitors of CSF secretion decreased PCSF-ISO by [~]30%. Shh-mediated cerebral-wall expansion and the resulting ventricular narrowing did not significantly increase PCSF-ISO. Removal of the brain-surrounding contractile tissues decreased PCSF-ISO by 80-90%. The intraamniotic pressure measured in utero (PAF-IU) was 1030.7 Pa. Our direct measurement revealed that the PCSF in utero (PCSF-IU) was 1076.4 Pa, confirming the susceptibility of PCSF to external factors. Subsequent PCSF measurements under hydrostatic pressure loading suggested that PCSF-IU = PCSF-ISO + PAF-IU, a relationship further used to estimate PCSF-IU at other ages when direct measurement was not possible. The estimated PCSF-IU decreased almost constantly from E10 to E16 (2000 500 Pa).

developmental biology↗

bioRxiv2023

Reciprocal inflammatory signals establish profibrotic cross-feeding metabolism

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung remodeling and collagen deposition that leads to respiratory failure. Myeloid cells are abundant in IPF lung and in murine lung fibrosis, but their functional effects are incompletely understood. Using mouse and human lung models, we show that ornithine produced by myeloid cells expressing Arg1 serves as a substrate for proline and collagen synthesis by lung fibroblasts. The predominant Arg1-expressing myeloid cells in mouse lung were macrophages, but in IPF lung, high-dimensional imaging revealed ARG1 to be expressed mainly in neutrophils. Arg1 inhibition suppressed both ornithine levels and collagen expression in cultured, precision-cut IPF lung slices and in murine lung fibrosis. These results were confirmed in macrophage-specific Arg1 KO mice. Furthermore, we find that this pathway is regulated by cell-to-cell crosstalk, starting with purinergic signaling: Fibroblast eATP receptor P2rx4 was necessary for fibroblast IL-6 expression, which in turn was necessary for Arg1 expression by myeloid cells. Taken together, our findings define an immune-mesenchymal circuit that governs profibrotic metabolism in lung fibrosis.

immunology↗