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Robust RBM3 and β-klotho expression in developing neurons in the human brain.

ABSTRACT: RNA binding motif 3 (RBM3) is a powerful neuroprotectant that inhibits neurodegenerative cell death in vivo and is a promising therapeutic target in brain ischemia. RBM3 is increased by the hormone fibroblast growth factor 21 (FGF21) in an age- and temperature-dependent manner in rat cortical neurons. FGF21 receptor binding is controlled by the transmembrane protein β-klotho, which is mostly absent in the adult brain. We discovered that RBM3/β-klotho is unexpectedly high in the human infant vs. adult brain (hippocampus/prefrontal cortex). The use of tissue homogenates in that study precluded a comparison of RBM3/β-klotho expression among different CNS cell-types, thus, omitted key evidence (i.e. confirmation of neuronal expression) that would otherwise provide a critical link to support their possible direct neuroprotective effects in humans. This report addresses that knowledge gap. High-quality fixed human hippocampus, cortex, and hypothalamic tissues were acquired from the NIH Neurobiobank (<1 yr (premature born) infants, 1 yr, 4 yr, and 34 yr). Dual labeling of cell-type markers vs. RBM3/β-klotho revealed enriched staining of targets in neurons in the developing brain. Identifying that RBM3/β-klotho is abundant in neurons in the immature brain is fundamentally important to guide protocol design and conceptual frameworks germane to future testing of these neuroprotective pathways in humans.

SUBMITTER: Jackson TC

PROVIDER: S-EPMC6890998 | biostudies-literature |

REPOSITORIES: biostudies-literature

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?-Klotho Expression in Human Tissues.

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Klotho inhibits neuronal senescence in human brain organoids.

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Chronological changes in microRNA expression in the developing human brain.

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Extrarenal α-klotho expression in human tissues

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2015-10-13 | PXD002775 | Pride

CXCR7 protein expression in human adult brain and differentiated neurons.

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Klotho inhibits neuronal senescence in human brain organoids

Project description:We report the application of brain organoids to study cellular senescence, in particular Klotho declining in expresssion mediates neuronal senescence, bulk RNA-sequencing further identified the potenital downstream target tha may modulate cellular senescence in the brain.

2021-04-09 | GSE171719 | GEO

Extrarenal ?-klotho expression in human tissues

Project description:?-Klotho has emerged as a powerful regulator of the ageing process. To-date, the expression profile of ?-Klotho in human tissues is unknown and its existence in some human tissue types is subject to much controversy. Objective: This is the first study to characterize system-wide tissue expression of transmembrane ?-Klotho in humans. We have employed next generation targeted proteomic analysis using Parallel Reaction Monitoring (PRM) in parallel with conventional antibody-based methods to determine the expression and spatial distribution of human ?-Klotho expression in health. Results: The distribution of ?-Klotho in human tissues from various organ systems, including arterial, epithelial, endocrine, reproductive and neuronal tissues was first identified by immunohistochemistry. Kidney tissues showed strong ?-Klotho expression, while liver did not reveal a detectable signal. These results were next confirmed by western blotting of both whole tissues and primary cells. To validate our antibody-based results, ?-Klotho expressing tissues were subjected to PRM mass spectrometry identifying peptides specific for the full length, transmembrane ?-Klotho isoform. Conclusions: The data presented confirms ?-Klotho expression in the kidney tubule and in artery, and provides evidence of ?-Klotho expression across organ systems and cell-types that have not previously been described in humans.

2017-03-29 | MSV000080719 | MassIVE

Tanc2-mediated mTOR inhibition balances mTORC1/2 signaling in the developing mouse brain and human neurons.

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| S-EPMC8113471 | biostudies-literature

Single-cell gene expression analysis reveals regulators of distinct cell subpopulations among developing human neurons.

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Expression and localisation of thymosin beta-4 in the developing human early fetal heart.

Project description:BackgroundThe objective of this study was to investigate the expression and localisation of thymosin β4 (Tβ4) in the developing human heart. Tβ4 is a cardioprotective protein which may have therapeutic potential. While Tβ4 is an endogenously produced protein with known importance during development, its role within the developing human heart is not fully understood. Elucidating the localisation of Tβ4 within the developing heart will help in understanding its role during cardiac development and is crucial for understanding its potential for cardioprotection and repair in the adult heart.MethodsExpression of Tβ4 mRNA in the early fetal human heart was assessed by PCR using both ventricular and atrial tissue. Fluorescence immunohistochemistry was used to assess the localisation of Tβ4 in sections of early fetal human heart. Co-staining with CD31, an endothelial cell marker, and with myosin heavy chain, a cardiomyocyte marker, was used to determine whether Tβ4 is localised to these cell types within the early fetal human heart.ResultsTβ4 mRNA was found to be expressed in both the atria and the ventricles of the early fetal human heart. Tβ4 protein was found to be primarily localised to CD31-expressing endothelial cells and the endocardium as well as being present in the epicardium. Tβ4-associated fluorescence was greater in the compact layer of the myocardial wall and the interventricular septum than in the trabecular layer of the myocardium.ConclusionsThe data presented illustrates expression of Tβ4 in the developing human heart and demonstrates for the first time that Tβ4 in the human heart is primarily localised to endothelial cells of the cardiac microvasculature and coronary vessels as-well as to the endothelial-like cells of the endocardium and to the epicardium.

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