Unlabelled: Molecular oxygen (O ) is one of the most functionally relevant metabolites. O is essential for mito-chondrial aerobic respiration. Changes in O affect muscle metabolism and play a critical role in the maintenance of skeletal muscle mass, with lack of sufficient O resulting in detrimental loss of muscle mass and function. How exactly O is used by muscle cells is less known, mainly due to the lack of tools to address O dynamics at the cellular level. Here we discuss a new imaging method for the real time quantification of intracellular O in muscle cells based on a genetically encoded O -responsive sensor, Myoglobin-mCherry. We show that we can spatially resolve and quantify intracellular O concentration in single muscle cells and that the spatiotemporal O gradient measured by the sensor is linked to, and reflects, functional metabolic changes occurring during the process of muscle differentiation.
Highlights: Real time quantitation of intracellular oxygen with spatial resolutionIdentification of metabolically active sites in single cellsOxygen metabolism is linked to muscle differentiation.
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http://dx.doi.org/10.1101/2023.07.18.548845 | DOI Listing |
Development
January 2025
Institute of Molecular Biology, Hannover Medical School, 30625 Hannover, Germany.
In the mammalian ureters, the lamina propria presents as a prominent layer of connective tissue underneath the urothelium. Despite its important structural and signaling functions, little is known how the lamina propria develops. Here, we show that in the murine ureter, the lamina propria arises at late fetal stages and massively increases by fibrocyte proliferation and collagen deposition after birth.
View Article and Find Full Text PDFImmunol Invest
January 2025
Department of Respiratory Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.
Introduction: T helper 17 (Th17) cells have a significant effect in the pathogenesis of asthma, and signal transducer and activator of transcription 3 (STAT3) pathway activation is critical for Th17 cell differentiation. Timosaponin A-III (TA3) was reported to inhibit the STAT3 pathway. Here, we investigated whether TA3 improved asthma by inhibiting the STAT3 pathway.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell-mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1+ macrophages mainly located in the intima in the aortic roots and ascending aortas of Fbn1C1041G/+ mice, further validated in MFS patients.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
January 2025
British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, United Kingdom. (M.W., M.F., R.O., L.S., M.M., C.M.S.).
Background: The ECM (extracellular matrix) provides the microenvironmental niche sensed by resident vascular smooth muscle cells (VSMCs). Aging and disease are associated with dramatic changes in ECM composition and properties; however, their impact on the VSMC phenotype remains poorly studied.
Methods: Here, we describe a novel in vitro model system that utilizes endogenous ECM to study how modifications associated with age and metabolic disease impact the VSMC phenotype.
ACS Pharmacol Transl Sci
January 2025
Laboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
The accumulation of ceramides and related metabolites has emerged as a pivotal mechanism contributing to the onset of age-related diseases. However, small molecule inhibitors targeting the ceramide synthesis pathway for clinical use are currently unavailable. We synthesized a safe and orally bioavailable inhibitor, termed ALT-007, targeting the rate-limiting enzyme of ceramide synthesis, serine palmitoyltransferase (SPT).
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