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Scientific Reports Jul 2021While classical cannabinoid receptors are known to crucially impact on myocardial infarction (MI) repair, a function of the cannabinoid-sensitive receptor GPR55 herein...
While classical cannabinoid receptors are known to crucially impact on myocardial infarction (MI) repair, a function of the cannabinoid-sensitive receptor GPR55 herein is poorly understood. We investigated the role of GPR55 in cardiac physiology and post-MI inflammation and remodelling. Global GPR55-/- and wildtype (WT) mice were basally characterized or assigned to 1, 3 or 28 days permanent MI and subsequently analysed via pro-inflammatory and pro-hypertrophic parameters. GPR55-/- deficiency was basally associated with bradycardia, increased diastolic LV volume and sarcomere length and a subtle inflammatory phenotype. While infarct size and myeloid cell infiltration were unaffected by GPR55 depletion, acute cardiac chemokine production was prolonged post-MI. Concurrently, GPR55-/- hearts exhibited a premature expansion of pro-reparative and phagocytic macrophages paralleled by early up-regulation of extracellular matrix (ECM) factors 3 days post-MI, which could be mimicked by sole haematopoietic GPR55 depletion. Moreover, global GPR55 deficiency mitigated MI-induced foetal gene re-programming and cardiomyocyte hypertrophy, culminating in aggravated LV dilatation and infarct expansion. GPR55 regulates cardiac homeostasis and ischaemia responses by maintaining adequate LV filling and modulating three crucial processes post-MI: wound healing kinetics, cardiomyocyte hypertrophy and maladaptive remodelling.
Topics: Animals; Biomimetics; Diastole; Health Status; Hematopoietic Stem Cell Transplantation; Hematopoietic System; Male; Mice; Myocardial Infarction
PubMed: 34257332
DOI: 10.1038/s41598-021-93755-y -
Clinical, Cosmetic and Investigational... 2022The purpose of this study was to explore the expression of TNF-α and NF-κB/p65 in Lichen planus skin lesions and their correlation with the pathogenesis of Lichen planus.
PURPOSE
The purpose of this study was to explore the expression of TNF-α and NF-κB/p65 in Lichen planus skin lesions and their correlation with the pathogenesis of Lichen planus.
PATIENTS AND METHODS
The case group consisted of 30 individuals diagnosed with LP based on clinical and histopathologic examination. The control group consisted of 10 individuals from an Orthopedic Department with normal skin. TNF-α and NF-κB/p65 expression in skin tissue samples was detected by immunohistochemistry.
RESULTS
The immunohistochemical results showed that TNF-α and NF-κB/p65 expression levels were significantly higher in LP skin lesions than normal skin tissues (P ≤ 0.05). Positive TNF-α staining mainly occurred in the cytoplasm of keratinocytes of the stratum granulosum, stratum spinosum, and stratum basale in the epidermis and lymphocytes in the superficial dermis. Positive NF-κB/p65 staining mainly occurred in the nucleus and cytoplasm of keratinocytes of the stratum spinosum and stratum basale in the epidermis and lymphocytes in the superficial dermis.
CONCLUSION
TNF-α and NF-κB/p65 are overexpressed in cutaneous LP. The two are positively correlated in LP, suggesting that they both play essential roles in the pathogenesis of LP.
PubMed: 35941857
DOI: 10.2147/CCID.S372662 -
Nature Communications May 2023The spatial sorting of RNA transcripts is fundamental for the refinement of gene expression to distinct subcellular regions. Although, in non-mammalian early...
The spatial sorting of RNA transcripts is fundamental for the refinement of gene expression to distinct subcellular regions. Although, in non-mammalian early embryogenesis, differential RNA localisation presages cell fate determination, in mammals it remains unclear. Here, we uncover apical-to-basal RNA asymmetries in outer blastomeres of 16-cell stage mouse preimplantation embryos. Basally directed RNA transport is facilitated in a microtubule- and lysosome-mediated manner. Yet, despite an increased accumulation of RNA transcripts in basal regions, higher translation activity occurs at the more dispersed apical RNA foci, demonstrated by spatial heterogeneities in RNA subtypes, RNA-organelle interactions and translation events. During the transition to the 32-cell stage, the biased inheritance of RNA transcripts, coupled with differential translation capacity, regulates cell fate allocation of trophectoderm and cells destined to form the pluripotent inner cell mass. Our study identifies a paradigm for the spatiotemporal regulation of post-transcriptional gene expression governing mammalian preimplantation embryogenesis and cell fate.
Topics: Mice; Animals; RNA; Embryo, Mammalian; Cell Differentiation; Blastocyst; Embryonic Development; Gene Expression Regulation, Developmental; Mammals
PubMed: 37253716
DOI: 10.1038/s41467-023-38436-2 -
Developmental Cell Jul 2019Mechanical forces are critical regulators of cell shape changes and developmental morphogenetic processes. Forces generated along the epithelium apico-basal cell axis...
Mechanical forces are critical regulators of cell shape changes and developmental morphogenetic processes. Forces generated along the epithelium apico-basal cell axis have recently emerged as essential for tissue remodeling in three dimensions. Yet the cellular machinery underlying those orthogonal forces remains poorly described. We found that during Drosophila leg folding cells eventually committed to die produce apico-basal forces through the formation of a dynamic actomyosin contractile tether connecting the apical surface to a basally relocalized nucleus. We show that the nucleus is anchored to basal adhesions by a basal F-actin network and constitutes an essential component of the force-producing machinery. Finally, we demonstrate force transmission to the apical surface and the basal nucleus by laser ablation. Thus, this work reveals that the nucleus, in addition to its role in genome protection, actively participates in mechanical force production and connects the contractile actomyosin cytoskeleton to basal adhesions.
Topics: Actins; Actomyosin; Animals; Apoptosis; Cell Adhesion; Cell Nucleus; Cytoskeleton; Drosophila melanogaster; Epithelium; Female; Male; Morphogenesis
PubMed: 31204174
DOI: 10.1016/j.devcel.2019.05.027 -
IUBMB Life Jan 2007Glutathiolation has emerged as an important post-translational modification that regulates protein function. Reduced glutathione remains bound to reactive cysteine side... (Review)
Review
Glutathiolation has emerged as an important post-translational modification that regulates protein function. Reduced glutathione remains bound to reactive cysteine side chains of several intracellular proteins even under basal conditions and the abundance of glutathiolated proteins increases upon oxidant challenge. Although protein glutathiolation was considered primarily to be a protective mechanism for preventing irreversible oxidation of protein thiols, recent evidence suggests that controlled glutathiolation reactions can also be used to modify protein structure and function. Several growth factors and cytokines promote protein glutathiolation and glutathiolated proteins have been shown to increase upon physiological stimulation of NO production. Given the high affinity of some nitrosylated proteins for glutathione, glutathiolation may also be a significant metabolic fate of nitrosylated proteins. Enzymatic pathways of protein de-glutathiolation have also been described; indicating that both glutathiolation and de-glutathiolation may be tightly regulated processes. In this review, we discuss the mechanisms of protein glutathiolation and how physiologic glutathiolation of specific proteins could regulate glucose metabolism, calcium homeostasis and changes in cell shape and contraction. We propose that glutathiolation represents a discrete sub-state within complex thiol-based redox circuits, relays and switches that regulate protein function basally and, upon oxidative stress, elicit adaptive responses or trigger cell death.
Topics: Animals; Glutathione; Humans; Nitric Oxide; Protein Processing, Post-Translational; Proteins
PubMed: 17365176
DOI: 10.1080/15216540701196944 -
Current Biology : CB Feb 2022Epithelial tissues are lined with a sheet-like basement membrane (BM) extracellular matrix at their basal surfaces that plays essential roles in adhesion and signaling....
Epithelial tissues are lined with a sheet-like basement membrane (BM) extracellular matrix at their basal surfaces that plays essential roles in adhesion and signaling. BMs also provide mechanical support to guide morphogenesis. Despite their importance, we know little about how epithelial cells secrete and assemble BMs during development. BM proteins are sorted into a basolateral secretory pathway distinct from other basolateral proteins. Because BM proteins self-assemble into networks, and the BM lines only a small portion of the basolateral domain, we hypothesized that the site of BM protein secretion might be tightly controlled. Using the Drosophila follicular epithelium, we show that kinesin-3 and kinesin-1 motors work together to define this secretion site. Similar to all epithelia, the follicle cells have polarized microtubules (MTs) along their apical-basal axes. These cells collectively migrate, and they also have polarized MTs along the migratory axis at their basal surfaces. We find follicle cell MTs form one interconnected network, which allows kinesins to transport Rab10+ BM secretory vesicles both basally and to the trailing edge of each cell. This positions them near the basal surface and the basal-most region of the lateral domain for exocytosis. When kinesin transport is disrupted, the site of BM protein secretion is expanded, and ectopic BM networks form between cells that impede migration and disrupt tissue architecture. These results show how epithelial cells can define a subdomain on their basolateral surface through MT-based transport and highlight the importance of controlling the exocytic site of network-forming proteins.
Topics: Animals; Basement Membrane; Drosophila; Drosophila Proteins; Epithelial Cells; Kinesins; Membrane Proteins
PubMed: 35021047
DOI: 10.1016/j.cub.2021.12.025 -
Neural Development Nov 2011The size and cell number of each brain region are influenced by the organization and behavior of neural progenitor cells during embryonic development. Recent studies on...
BACKGROUND
The size and cell number of each brain region are influenced by the organization and behavior of neural progenitor cells during embryonic development. Recent studies on developing neocortex have revealed the presence of neural progenitor cells that divide away from the ventricular surface and undergo symmetric divisions to generate either two neurons or two progenitor cells. These 'basal' progenitor cells form the subventricular zone and are responsible for generating the majority of neocortical neurons. However, not much has been studied on similar types of progenitor cells in other brain regions.
RESULTS
We have identified and characterized basal progenitor cells in the embryonic mouse thalamus. The progenitor domain that generates all of the cortex-projecting thalamic nuclei contained a remarkably high proportion of basally dividing cells. Fewer basal progenitor cells were found in other progenitor domains that generate non-cortex projecting nuclei. By using intracellular domain of Notch1 (NICD) as a marker for radial glial cells, we found that basally dividing cells extended outside the lateral limit of radial glial cells, indicating that, similar to the neocortex and ventral telencephalon, the thalamus has a distinct subventricular zone. Neocortical and thalamic basal progenitor cells shared expression of some molecular markers, including Insm1, Neurog1, Neurog2 and NeuroD1. Additionally, basal progenitor cells in each region also expressed exclusive markers, such as Tbr2 in the neocortex and Olig2 and Olig3 in the thalamus. In Neurog1/Neurog2 double mutant mice, the number of basally dividing progenitor cells in the thalamus was significantly reduced, which demonstrates the roles of neurogenins in the generation and/or maintenance of basal progenitor cells. In Pax6 mutant mice, the part of the thalamus that showed reduced Neurog1/2 expression also had reduced basal mitosis.
CONCLUSIONS
Our current study establishes the existence of a unique and significant population of basal progenitor cells in the thalamus and their dependence on neurogenins and Pax6. These progenitor cells may have important roles in enhancing the generation of neurons within the thalamus and may also be critical for generating neuronal diversity in this complex brain region.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Eye Proteins; Female; Gene Expression Regulation, Developmental; Homeodomain Proteins; Male; Mice; Mice, Transgenic; Neocortex; Nerve Tissue Proteins; Neural Stem Cells; Neurons; PAX6 Transcription Factor; Paired Box Transcription Factors; Pregnancy; Repressor Proteins; Thalamus; Transcription Factors
PubMed: 22077982
DOI: 10.1186/1749-8104-6-35 -
Bio-protocol Mar 2022Mitochondria are relatively small, fragmented, and abundant in the large embryos of and zebrafish. It is essential to study their distribution and dynamics in these...
Mitochondria are relatively small, fragmented, and abundant in the large embryos of and zebrafish. It is essential to study their distribution and dynamics in these embryos to understand the mechanistic role of mitochondrial function in early morphogenesis events. Photoactivation of mitochondrially tagged GFP (mito-PA-GFP) is an attractive method to highlight a specific population of mitochondria in living embryos and track their distribution during development. embryos contain large numbers of maternally inherited mitochondria, which distribute differently at specific stages of early embryogenesis. They are enriched basally in the syncytial division cycles and move apically during cellularization. Here, we outline a method for highlighting a population of mitochondria in discrete locations using mito-PA-GFP in the blastoderm embryo, to follow their distribution across syncytial division cycles and cellularization. Photoactivation uses fluorophores, such as PA-GFP, that can change their fluorescence state upon exposure to ultraviolet light. This enables marking a precise population of fluorescently tagged molecules of organelles at selected regions, to visualize and systematically follow their dynamics and movements. Photoactivation followed by live imaging provides an effective way to pulse label a population of mitochondria and follow them through the dynamic morphogenetic events during embryogenesis.
PubMed: 35592607
DOI: 10.21769/BioProtoc.4347 -
Annals of Botany Sep 2007Understanding the mode and mechanisms of the evolution of the angiosperm flower is a long-standing and central problem of evolutionary biology and botany. It has... (Review)
Review
BACKGROUND
Understanding the mode and mechanisms of the evolution of the angiosperm flower is a long-standing and central problem of evolutionary biology and botany. It has essentially remained unsolved, however. In contrast, considerable progress has recently been made in our understanding of the genetic basis of flower development in some extant model species. The knowledge that accumulated this way has been pulled together in two major hypotheses, termed the 'ABC model' and the 'floral quartet model'. These models explain how the identity of the different types of floral organs is specified during flower development by homeotic selector genes encoding transcription factors.
SCOPE
We intend to explain how the 'ABC model' and the 'floral quartet model' are now guiding investigations that help to understand the origin and diversification of the angiosperm flower.
CONCLUSIONS
Investigation of orthologues of class B and class C floral homeotic genes in gymnosperms suggest that bisexuality was one of the first innovations during the origin of the flower. The transition from dimer to tetramer formation of floral homeotic proteins after establishment of class E proteins may have increased cooperativity of DNA binding of the transcription factors controlling reproductive growth. That way, we hypothesize, better 'developmental switches' originated that facilitated the early evolution of the flower. Expression studies of ABC genes in basally diverging angiosperm lineages, monocots and basal eudicots suggest that the 'classical' ABC system known from core eudicots originated from a more fuzzy system with fading borders of gene expression and gradual transitions in organ identity, by sharpening of ABC gene expression domains and organ borders. Shifting boundaries of ABC gene expression may have contributed to the diversification of the angiosperm flower many times independently, as may have changes in interactions between ABC genes and their target genes.
Topics: Biological Evolution; Flowers; Magnoliopsida
PubMed: 17670752
DOI: 10.1093/aob/mcm143 -
Viruses Jan 2023Mitoviruses are small vertically transmitted RNA viruses found in fungi, plants and animals. Taxonomically, a total of 105 species and 4 genera have been formally...
Mitoviruses are small vertically transmitted RNA viruses found in fungi, plants and animals. Taxonomically, a total of 105 species and 4 genera have been formally recognized by ICTV, and recently, 18 new putative species have been included in a new proposed genus. Transcriptomic and metatranscriptomic studies are a major source of countless new virus-like sequences that are continually being added to open databases and these may be good sources for identifying new putative mitoviruses. The search for mitovirus-like sequences in the NCBI databases resulted in the discovery of more than one hundred new putative mitoviruses, with important implications for taxonomy and also for the evolutionary scenario. Here, we propose the inclusion of four new putative members to the genus , and the existence of a new large basally divergent lineage composed of 144 members that lack internal UGA codons (subfamily "Arkeomitovirinae"), a feature not shared by the vast majority of mitoviruses. Finally, a taxonomic categorization proposal and a detailed description of the evolutionary history of mitoviruses were carried out. This in silico study supports the hypothesis of the existence of a basally divergent lineage that could have had an impact on the early evolutionary history of mitoviruses.
Topics: Animals; Reading Frames; Codon, Terminator; Biological Evolution; Databases, Factual; Gene Expression Profiling; Magnoliopsida
PubMed: 36851553
DOI: 10.3390/v15020340