scholarly journals Inhibition of BMP and FGF signaling prior to wound epithelium formation leads to an aberrant regenerative response in teleost fish Poecilia latipinna

2021 ◽  
Author(s):  
Isha Ranadive ◽  
Sonam Patel ◽  
Siddharth Pai ◽  
Kashmira Khaire ◽  
Suresh Balakrishnan
Keyword(s):  
Cell Death ◽  
Teleost Fish ◽  
The Other ◽  
Fgf Signaling ◽  
Caudal Fin ◽  
Fin Regeneration ◽  
Blastema Formation ◽  
Messenger Molecules ◽  
Wound Epithelium

The BMP and FGF pathways play a pivotal role in the successful regeneration of caudal fin of teleost fish. Individual inhibition of these pathways led to impaired caudal fin regeneration until the pharmacologic inhibitor of FGF (SU5402) and BMP (LDN193189) were metabolized off. Therefore, in the current study both these pathways were inhibited collectively wherein inhibition of BMP and FGF during the wound epithelium formation led to stalling of the process by bringing down the established levels of shh and runx2. In members of the treatment group, it was observed that, each blastema grows crouched rather than linear and the regrown lepidotrichia therefore remain tilted down. Amongst the other irregularities observed, the transition from epithelial to mesenchymal cells was found hindered due to down-regulation of snail and twist, brought about by BMP and FGF inhibition. Compromised expression of Snail and twist deranged the normal levels of cadherins causing disruption in the transition of cells. Lastly, blocking BMP and FGF delayed blastema formation and proliferation due to diminished levels of fgf2, fgf8, fgf10 and bmp6, while casp3 and casp9 levels remained heightened causing accelerated cell death. This study not only highlights the axial role of BMP and FGF pathways in regeneration but also accentuates the collaboration amongst the two. This ingenious coordination of signalling further reinforces the involvement of relaying messenger molecules between these crucial pathways.

Cell cycle controls and the role of nerves and the regenerate epithelium in urodele forelimb regeneration: possible modifications of basic concepts

1987 ◽  
Vol 65 (8) ◽  
pp. 739-749 ◽  
Author(s):  
Roy A. Tassava ◽  
David J. Goldhamer ◽  
Bruce L. Tomlinson
Keyword(s):  
Cell Cycle ◽  
Monoclonal Antibody ◽  
Limb Regeneration ◽  
Blastema Formation ◽  
Basic Concepts ◽  
Regenerate Epithelium ◽  
Early Wound ◽  
Skin Epidermis ◽  
Wound Epithelium

Data from pulse and continuous labeling with [3H]thymidine and from studies with monoclonal antibody WE3 have led to the modification of existing models and established concepts pertinent to understanding limb regeneration. Not all cells of the adult newt blastema are randomly distributed and actively progressing through the cell cycle. Instead, many cells are in a position that we have designated transient quiescence (TQ) and are not actively cycling. We postulate that cells regularly leave the TQ population and enter the actively cycling population and vice versa. The size of the TQ population may be at least partly determined by the quantity of limb innervation. Larval Ambystoma may have only a small or nonexisting TQ, thus accounting for their rapid rate of regeneration. Examination of reactivity of monoclonal antibody WE3 suggests that the early wound epithelium, which is derived from skin epidermis, is later replaced by cells from skin glands concomitant with blastema formation. WE3 provides a useful tool to further investigate the regenerate epithelium.

scholarly journals Two Different Transgenes to Study Gene Silencing and Re-Expression During Zebrafish Caudal Fin and Retinal Regeneration

2006 ◽  
Vol 6 ◽  
pp. 65-81 ◽  
Author(s):  
Ryan Thummel ◽  
Christopher T. Burket ◽  
David R. Hyde
Keyword(s):  
Tissue Regeneration ◽  
Transgene Expression ◽  
Egfp Expression ◽  
Transgenic Zebrafish ◽  
Retinal Regeneration ◽  
Caudal Fin ◽  
Fin Regeneration ◽  
Differentiated Cells ◽  
Neuronal Progenitors ◽  
Wound Epithelium

We used the 500-bpXenopusef1-α promoter and the 2-kb zebrafish histone2A.F/Zpromoter to generate several independent transgenic zebrafish lines expressing EGFP. While both promoters drive ubiquitous EGFP expression in early zebrafish development, they are systematically silenced in several adult tissues, including the retina and caudal fin. However, EGFP expression is temporarily renewed in the adult during either caudal fin or retinal regeneration. In the Tg(H2A.F/Z:EGFP)ntline, EGFP is moderately expressed in both the wound epithelium and blastema of the regenerating caudal fin. In the Tg(ef1-α:EGFP)ntline, EGFP expression is reinitiated and restricted to the blastema of the regenerating caudal fin and colabels with BrdU, PCNA, andmsxc-positive cells. Thus, these two ubiquitous promoters drive EGFP transgene expression in different cell populations during caudal fin regeneration. We further analyzed the ability of theef1-α:EGFPtransgene to label nonterminally differentiated cells during adult tissue regeneration. First, we demonstrated that the transgene is highly methylated in adult zebrafish caudal fin tissue, but not during fin regeneration, implicating methylation as a potential means of transgene silencing in this line. Next, we determined that theef1-α:EGFPtransgene is also re-expressed during adult retinal regeneration. Specifically, theef1-α:EGFPtransgene colabels with PCNA in the Müglia, a specialized cell that is the source of neuronal progenitors during zebrafish retinal regeneration. Thus, we concluded that Tg(ef1-α:EGFP)nt line visually marks nonterminally differentiated cells in multiple adult regeneration environments and may prove to be a useful marker in tissue regeneration studies in zebrafish.

Regeneration and pattern formation in planarians. II. and role of cell movements in blastema formation

Development ◽  
1989 ◽  
Vol 107 (1) ◽  
pp. 69-76 ◽  
Author(s):  
E. Salo ◽  
J. Baguna
Keyword(s):  
Pattern Formation ◽  
Cell Movement ◽  
Formation Mechanisms ◽  
Blastema Formation ◽  
Chromosomal Markers ◽  
Undifferentiated Cells ◽  
Local Cell ◽  
Number Of Cells ◽  
Wound Epithelium

In planarians, blastema cells do not divide, and growth blastema is thought to result from the steady wound epithelium, of undifferentiated cells produced in the stump. However, whether these cells come only sources or whether cells placed far from the wound can participate, after long-range migrations, in the still uncertain. To study this problem, we have parameters of the process of regeneration: cell growth; number of cells produced by mitosis in the wound (postblastema); and rates of movement undifferentiated cells using grafting procedures with chromosomal markers. The results show that: (1) cells area spread (move) at higher rates than cells placed (90–140_mday-1 versus 40–50_mday-1); (2) cells than 500_m from the wound boundary are hardly 5-day-old blastemata; and (3) the number of cells within a 200–300_m postblastema area around the wound explain, provided their rates of movement are taken increasing number of blastema cells. From this, it is blastema cells in planarians originate from local mitotic activity jointly with local cell movement postblastema area around the wound match the blastema cells during regeneration. The implications for blastema growth and pattern formation mechanisms

scholarly journals Excessive phospholipid peroxidation distinguishes ferroptosis from other cell death modes including pyroptosis

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Bartosz Wiernicki ◽  
Hanne Dubois ◽  
Yulia Y. Tyurina ◽  
Behrouz Hassannia ◽  
Hülya Bayir ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
The Other ◽  
Strong Increase ◽  
Oxygen Species ◽  
Membrane Rupture ◽  
Regulated Cell Death ◽  
Phospholipid Peroxidation ◽  
Differential Involvement

Abstract Lipid peroxidation (LPO) drives ferroptosis execution. However, LPO has been shown to contribute also to other modes of regulated cell death (RCD). To clarify the role of LPO in different modes of RCD, we studied in a comprehensive approach the differential involvement of reactive oxygen species (ROS), phospholipid peroxidation products, and lipid ROS flux in the major prototype modes of RCD viz. apoptosis, necroptosis, ferroptosis, and pyroptosis. LC-MS oxidative lipidomics revealed robust peroxidation of three classes of phospholipids during ferroptosis with quantitative predominance of phosphatidylethanolamine species. Incomparably lower amounts of phospholipid peroxidation products were found in any of the other modes of RCD. Nonetheless, a strong increase in lipid ROS levels was detected in non-canonical pyroptosis, but only during cell membrane rupture. In contrast to ferroptosis, lipid ROS apparently was not involved in non-canonical pyroptosis execution nor in the release of IL-1β and IL-18, while clear dependency on CASP11 and GSDMD was observed. Our data demonstrate that ferroptosis is the only mode of RCD that depends on excessive phospholipid peroxidation for its cytotoxicity. In addition, our results also highlight the importance of performing kinetics and using different methods to monitor the occurrence of LPO. This should open the discussion on the implication of particular LPO events in relation to different modes of RCD.

Role of Hox genes in zebrafish caudal fin regeneration

2006 ◽  
Vol 25 ◽  
pp. S25-S25
Author(s):  
M SARRASJR ◽  
R THUMMEL ◽  
A GODMAN
Keyword(s):  
Hox Genes ◽  
Caudal Fin ◽  
Fin Regeneration

scholarly journals Understanding the complexity of Epimorphic Regeneration in zebrafish: A Transcriptomic and Proteomic approach.

2021 ◽  
Author(s):  
Sarena Banu ◽  
Namami Gaur ◽  
Sowmy Nair ◽  
Tanuja Ravikrishnan ◽  
Shahida Khan ◽  
...  
Keyword(s):  
Differential Expression Analysis ◽  
Cell Movement ◽  
Molecular Transport ◽  
Caudal Fin ◽  
Tissue Samples ◽  
Fin Regeneration ◽  
Epimorphic Regeneration ◽  
Proteomic Approach ◽  
Generation Sequencing

Genomic and Proteomic changes play a crucial role in perpetuating regeneration of complex tissues through differentiation and growth. The complex Epimorphic regeneration of zebrafish caudal fin tissue is hasty and absolute. This study was executed to understand the role of various genes/proteins involved in the regeneration of zebrafish caudal fin tissue through differential expression analysis. High throughput transcriptomics analysis involving Next Generation Sequencing approach and iTRAQ based quantitative proteomics analyses were performed on the regenerating tissue samples for various regenerating time points. Based on our study 1408 genes and 661 proteins were found differentially regulated in the regenerating caudal fin tissue for having at least 1-log fold change in their expression at 12hpa, 1, 2, 3 and 7dpa stages against control non-regenerating tissue. Interleukin, SLC, PRMT, HOX, neurotransmitter and several novel genes were found to be associated with regeneration for its differential regulation during the mechanism. Based on the network and pathway analysis the differentially regulated genes and proteins were found allied with activation of cell proliferation, cell viability, cell survival & cell movement and inactivation of organismal death, morbidity, necrosis, death of embryo & cell death. Network pathways such as Cancer & development disorder, Cell signaling molecular transport, organismal injury & abnormalities and Cellular development, growth & proliferation were found most significantly associated with the zebrafish caudal fin regeneration mechanism. This study has mapped a detailed insight of the genes/proteins expression associated with the epimorphic regeneration more profoundly.

Displacement of Bim From Anti-Apoptotic Proteins Is the Primary Factor for Determining ABT-737 Activity in Multiple Myeloma Cell Lines.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2851-2851
Author(s):  
Alejo A Morales ◽  
Metin Kurtoglu ◽  
David Siefker ◽  
Shannon M Matulis ◽  
Delia M Gutman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Cell Lines ◽  
Cell Types ◽  
Myeloma Cell ◽  
Resistant Cell ◽  
The Other ◽  
Multiple Myeloma Cell ◽  
Other Hand

Abstract Abstract 2851 Poster Board II-827 ABT-737 and its orally active analog ABT-263 are Bcl-2-family inhibitors that are currently in clinical trials for a variety of cancers including hematological malignancies such as multiple myeloma. Previously, we reported that the sensitivity of multiple myeloma cell lines to ABT-737 correlates with the interactions, but not the expression, of Bcl-2 proteins. Analysis of 6 multiple myeloma cell lines revealed that expression of Bcl-2 proteins did not correlate with sensitivity, however the sensitive cells (8226/S, MM.1S and KMS-11) have a substantial amount of their pro-apoptotic Bcl-2 protein, Bak, bound to Bcl-xL. On the other hand, in the insensitive cell lines (U266, KMS-11 and OPM2), Bak was found to be associated with Mcl-1, a family member that does not bind ABT-737 and thereby confers resistance to this drug. Furthermore, we also showed that release of the BH3-only protein Bim by ABT-737 from Bcl-xL and Bcl-2 also contributes to cell death in 8226/S and MM.1S. The purpose of the current study is to further investigate the role of Bim in ABT-737-induced cell death in the multiple myeloma lines. Similar to Bak, a substantial amount of Bim is bound to Bcl-xL and Bcl-2 in the ABT-737-sensitive cell lines, MM.1S and KMS-18, while in the insensitive cell lines, it is highly bound to Mcl-1. Surprisingly, in the ABT-737-sensitive 8226/S cells, Bim appears to bind to Mcl-1. However in these cells, ABT-737 treatment resulted in upregulation of Noxa, which is a BH3-only protein that binds Mcl-1 and can release Bim. Taken together these data suggest that although binding of Bim to Mcl-1 may confer resistance to ABT-737, in certain cell types this treatment could also induce Noxa expression that antagonizes Mcl-1-mediated resistance. Consistent with this hypothesis, Mcl-1 overexpression as well as knockdown of Noxa expression significantly protected 8226/S cells from ABT-737-induced cell death while they had no effect in MM.1S cells. To further demonstrate the role of Bim in ABT-737-induced cell death, ABT-resistant 8226/S, KMS-11, KMS-18 and U266 cell lines were generated. In the resistant cell lines of 8226/S and KMS-18, Bim is exclusively bound to Mcl-1, which was overexpressed as compared to the parental cells. Bak binding was not affected by acquisition of ABT-737 resistance. This result is in agreement with the findings that interaction of Bim and Mcl-1 confers resistance to ABT-737. On the other hand, in ABT-resistant U266 and KMS-11 cell lines, Bim expression was down-regulated while Mcl-1 levels were not changed. Thus, it appears that in cells where Bim is already bound to Mcl-1, further resistance is achieved by down-regulating the expression of this BH3-only protein. Overall, these results suggest that the complex interactions between Bcl-2 proteins need to be investigated in order to understand how multiple myeloma cells may respond to ABT-737 treatment. Disclosures: Boise: University of Chicago: Patents & Royalties.

Role of annexin gene and its regulation during zebrafish caudal fin regeneration

2016 ◽  
Vol 24 (3) ◽  
pp. 551-559 ◽  
Author(s):  
Sandeep Saxena ◽  
Sruthi Purushothaman ◽  
Vuppalapaty Meghah ◽  
Bhawna Bhatti ◽  
Akhila Poruri ◽  
...  
Keyword(s):  
Caudal Fin ◽  
Fin Regeneration ◽  
Annexin Gene

scholarly journals Functional Role of Annexins in Zebrafish Caudal Fin Regeneration – A Gene Knockdown Approach in Regenerating Tissue

2018 ◽  
Author(s):  
Mir Quoseena ◽  
Sowmya Vuppaladadium ◽  
Shahid Hussain ◽  
Swarna Bharathi ◽  
Mohammed M Idris
Keyword(s):  
Functional Role ◽  
Target Genes ◽  
Human Beings ◽  
Caudal Fin ◽  
Fin Regeneration ◽  
Epimorphic Regeneration ◽  
Knock Down ◽  
Regeneration Mechanism ◽  
Almost All

AbstractRegeneration is an adaptive phenomenon with wide biological implications spread heterogeneously in almost all the organism including human beings. The ability of regeneration varies from species to species for its impediment. Epimorphic regeneration of zebrafish caudal fin tissue is most widely studied regeneration mechanism for its discrete and rapid regenerative capability. Several genes/proteins were found to be associated with zebrafish caudal fin tissue regeneration. Here, we have evaluated the functional role ofAnnexin 2aand2bgenes in adult zebrafish caudal fin tissue undergoing regeneration using a novel CRSISPR-Cas9 gene knock down approach. Knock down of both the genes individually elicited in decelerated regeneration and down regulation of target genes and its partner genes/proteins such as ANXA1a, ANXA5b and ANXA13. This study validates a novel gene targeting approach and the possible role of annexin in regeneration mechanism.

scholarly journals Role of Extracellular Vesicles in Cell Death and Inflammation

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2663
Author(s):  
Rahul Sanwlani ◽  
Lahiru Gangoda
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Tissue Damage ◽  
Lung Inflammation ◽  
The Body ◽  
The Other ◽  
Immune Mediators

Extracellular vesicles (EVs) have been identified as novel mediators of intercellular communication. They work via delivering the sequestered cargo to cells in the close vicinity, as well as distant sites in the body, regulating pathophysiological processes. Cell death and inflammation are biologically crucial processes in both normal physiology and pathology. These processes are indistinguishably linked with their effectors modulating the other process. For instance, during an unresolvable infection, the upregulation of specific immune mediators leads to inflammation causing cell death and tissue damage. EVs have gained considerable interest as mediators of both cell death and inflammation during conditions, such as sepsis. This review summarizes the types of extracellular vesicles known to date and their roles in mediating immune responses leading to cell death and inflammation with specific focus on sepsis and lung inflammation.

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