scholarly journals Fast transcriptional activation of developmental signalling pathways during wound healing of the calcareous sponge Sycon ciliatum

2021 ◽  
Author(s):  
Cuneyt Caglar ◽  
Alexander Ereskovsky ◽  
Mary Laplante ◽  
Daria Tokina ◽  
Sven Leininger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Developmental Pathways ◽  
Signalling Pathways ◽  
Collective Migration ◽  
Cell Transdifferentiation ◽  
Calcareous Sponge ◽  
Tgfβ Signalling ◽  
Early Wound

Background: The ability to regenerate lost or damaged body parts is an ancient animal characteristic with a wide yet variable distribution across all phyla. Sponges, likely the sister group to all other animals, have remarkable regenerative abilities including whole body regeneration and re-development from dissociated cells. The calcareous sponge Sycon ciliatum has been subject to various regeneration studies since the beginning of the last century. However, the early steps of wound healing of S. ciliatum have not been addressed from the molecular perspective. Results: In this study, we combined electron microscopy with gene expression analysis to investigate wound healing after transverse sectioning of S. ciliatum. Microscopic analysis revealed massive transdifferentiation and collective migration behaviour of choanocytes and pinacocytes early upon injury (6-12h) as the main mechanisms for quick closure of the wound surface. RNA-sequencing identified upregulation of components of the conserved metazoan Wnt and TGFβ signalling pathways within 3h, preceding morphologically detectable wound healing events. De novo upregulation after a decline in expression coincides with morphologically visible polarity establishment. Moreover, by integrating the new wound healing data set with previously published data derived from intact sponge, we demonstrate similarity between gene activity during early wound healing and osculum maintenance. Whole mount in situ hybridisation of the TGFβ signalling pathway ligand SciTGFβU and signal transducer SciSmadRa show that the early activation of both is initially encompassing a large area surrounding the cut surface with gradual restriction to the edge of the forming regenerative membrane as wound healing progresses. While SciTGFβU transcripts are localised to exo- and endopinacocytes, SciSmadRa expression appears across all cell types. Using an EdU cell proliferation assay, we found that a global increase in cell proliferation is not visible before 12h into wound healing. Hence, the initial stages to cover the injury site including cell transdifferentiation and migration seem to be executed by cells remaining after injury. Gene expression clustering coupled with GO term enrichment analysis confirmed that expression of genes involved in processes related to cell proliferation, DNA repair as well as apoptotic processes at 3 and 6h of wound healing was not upregulated. On the other hand, genes associated with positive regulation of transcription, signal transduction, actin filament and chromatin organisation, as well as the Wnt signalling pathway are upregulated at early wound healing stages. Conclusion: We have analysed wound healing in the calcareous sponge Sycon ciliatum using microscopic and genomic methods. This study highlights a remarkable mechanism of interplay between cell transdifferentiation and collective migration we hypothesise to be regulated by conserved metazoan developmental pathways and numerous taxonomically restricted genes. Expression of these genes in regenerating and intact sponges sheds light on the long-standing question whether embryonic developmental pathways are redeployed in regeneration.

Effect of a Synthetic Extracellular Matrix on Vocal Fold Lamina Propria Gene Expression in Early Wound Healing

2006 ◽  
Vol 12 (11) ◽  
pp. 3201-3207 ◽  
Author(s):  
Suzy Duflo ◽  
Susan L. Thibeault ◽  
Wenhua Li ◽  
Xiao Zheng Shu ◽  
Glenn Prestwich
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Lamina Propria ◽  
Vocal Fold ◽  
Early Wound

Effect of a Synthetic Extracellular Matrix on Vocal Fold Lamina Propria Gene Expression in Early Wound Healing

2006 ◽  
Vol 0 (0) ◽  
pp. 061012064037005 ◽  
Author(s):  
Suzy Duflo ◽  
Susan L. Thibeault ◽  
Wenhua Li ◽  
Xiao Zheng Shu ◽  
Glenn Prestwich
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Lamina Propria ◽  
Vocal Fold ◽  
Early Wound

Nutrient-regulated gene expression in eukaryotes

2006 ◽  
Vol 73 ◽  
pp. 85-96 ◽  
Author(s):  
Richard J. Reece ◽  
Laila Beynon ◽  
Stacey Holden ◽  
Amanda D. Hughes ◽  
Karine Rébora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Control ◽  
Direct Interaction ◽  
Signalling Pathways ◽  
A Cell ◽  
One Step ◽  
Higher Eukaryotes ◽  
Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

ACE INHIBITION ATTENUATES RENAL PDGF GENE EXPRESSION AND CELL PROLIFERATION IN SUBTOTAL NEPHRECTOMY

Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A104-A104
Author(s):  
Jandeleit‐Dahm K ◽  
Wu Ll ◽  
Johnson Rj ◽  
Cox Aj ◽  
Kelly Dj ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Ace Inhibition ◽  
Subtotal Nephrectomy

MOLECULAR CONTROL OF ARTICULAR CARTILAGE DEGENERATION BY TRANSFORMING GROWTH FACTOR ALPHA

2008 ◽  
Vol 31 (4) ◽  
pp. 2
Author(s):  
Tom Appleton ◽  
Shirine Usmani ◽  
John Mort ◽  
Frank Beier
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Growth Factor ◽  
P38 Mapk ◽  
Transforming Growth Factor ◽  
Cartilage Degeneration ◽  
Signalling Pathways ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha ◽  
Articular Cartilage Degeneration

Background: Articular cartilage degeneration is a hallmark of osteoarthritis (OA). We previously identified increased expression of transforming growth factor alpha (TGF?) and chemokine (C-C motif) ligand 2 (CCL2) in articular cartilage from a rat modelof OA (1,2). We subsequently reported that TGF? signalling modified chondrocyte cytoskeletal organization, increased catabolic and decreased anabolic gene expression and suppressed Sox9. Due to other roles in chondrocytes, we hypothesized that the effects ofTGF? on chondrocytes are mediated by Rho/ROCK and MEK/ERK signaling pathways. Methods: Primary cultures of chondrocytes and articularosteochondral explants were treated with pharmacological inhibitors of MEK1/2(U0126), ROCK (Y27632), Rho (C3), p38 MAPK (SB202190) and PI3K (LY294002) to elucidate pathway involvement. Results: Using G-LISA we determined that stimulation of primary chondrocytes with TGF? activates RhoA. Reciprocally, inhibition of RhoA/ROCK but not other signalling pathways prevents modification of the actin cytoskeleton in responseto TGF?. Inhibition of MEK/ERKsignaling rescued suppression of anabolic gene expression by TGF? including SOX9 mRNA and protein levels. Inhibition of MEK/ERK, Rho/ROCK, p38 MAPK and PI3K signalling pathways differentially controlled the induction of MMP13 and TNF? gene expression. TGF? also induced expression of CCL2 specifically through MEK/ERK activation. In turn, CCL2 treatment induced the expression of MMP3 and TNF?. Finally, we assessed cartilage degradation by immunohistochemical detection of type II collagen cleavage fragments generated by MMPs. Blockade of RhoA/ROCK and MEK/ERK signalling pathways reduced the generation of type IIcollagen cleavage fragments in response to TGF? stimulation. Conclusions: Rho/ROCK signalling mediates TGF?-induced changes inchondrocyte morphology, while MEK/ERK signalling mediates the suppression ofSox9 and its target genes, and CCL2 expression. CCL2, in turn, induces the expression of MMP3 and TNF?, two potent catabolic factors known to be involved in OA. These pathways may represent strategic targets for interventional approaches to treating cartilage degeneration in osteoarthritis. References: 1. Appleton CTG et al. Arthritis Rheum 2007;56:1854-68. 2. Appleton CTG et al. Arthritis Rheum 2007; 56:3693-705.

scholarly journals STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lionel Condé ◽  
Yulemi Gonzalez Quesada ◽  
Florence Bonnet-Magnaval ◽  
Rémy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

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