scholarly journals A Roadmap for Intestinal Regeneration

2020 ◽  
Vol 52 ◽  
Author(s):  
David Quispe-Parra ◽  
Griselle Valentín ◽  
José E. García-Arrarás
Keyword(s):  
Molecular Mechanism ◽  
Sea Cucumber ◽  
Regenerative Process ◽  
Research Model ◽  
Functional Studies ◽  
Cellular Processes ◽  
Sequencing Technologies ◽  
Cellular Events ◽  
Intestinal Regeneration ◽  
Holothuria Glaberrima

Regeneration of lost or injured organs is an intriguing process where numerous cellular events take place to form the new structure. Studies of this process during reconstitution of the intestine have been performed in echinoderms, particularly in holothurians. Many cellular events triggered during regeneration have been described using the sea cucumber Holothuria glaberrima as a research model. More recent experiments have targeted the molecular mechanism behind the process, a task that has been eased by the new sequencing technologies now available. In this review we present the studies involving cellular processes and the genes that have been identified to be associated with the early events of gut regeneration. We also present the ongoing efforts to perform functional studies necessary to establish the role(s) of the identified genes. A synopsis of the studies is given with the course of the regenerative process established so far.

scholarly journals Transcriptomic Analysis of Early Stages of Intestinal Regeneration in Holothuria glaberrima

2020 ◽  
Author(s):  
David J. Quispe-Parra ◽  
Joshua G. Medina-Feliciano ◽  
Sebastián Cruz-González ◽  
Humberto Ortiz-Zuazaga ◽  
José E. García-Arrarás
Keyword(s):  
De Novo ◽  
Focal Point ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Regenerative Process ◽  
Pathway Enrichment Analysis ◽  
Cellular Processes ◽  
Early Stages ◽  
Intestinal Regeneration ◽  
Holothuria Glaberrima

AbstractEchinoderms comprise a group of animals with impressive regenerative capabilities. They can replace complex internal organs following injury or autotomy. In holothurians or sea cucumbers, cellular processes of intestinal regeneration have been extensively studied. The molecular machinery behind this faculty, however, remains to be understood. Here we assembled and annotated a de novo transcriptome using RNA-seq data consisting of regenerating and non-regenerating intestinal tissues from the sea cucumber Holothuria glaberrima. Comparisons of differential expression were made using the mesentery as a reference against 24 hour and 3 days regenerating intestine, revealing a large number of differentially expressed transcripts. Gene ontology and pathway enrichment analysis showed evidence of increasing transcriptional activity. Further analysis of transcripts associated with transcription factors revealed diverse expression patterns with mechanisms involving developmental and cancer-related activity that could be related to the regenerative process. Our study demonstrates the broad and diversified gene expression profile during the early stages of the process using the mesentery as the focal point of intestinal regeneration. It also establishes the genes that are the most important candidates in the cellular processes that underlie regenerative responses.

scholarly journals Antibiotics Modulate Intestinal Regeneration

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 236
Author(s):  
Lymarie M. Díaz-Díaz ◽  
Natalia Rosario-Meléndez ◽  
Andrea Rodríguez-Villafañe ◽  
Yariel Y. Figueroa-Vega ◽  
Omar A. Pérez-Villafañe ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sea Cucumber ◽  
Regenerative Processes ◽  
Ecm Remodeling ◽  
Bacterial Cultures ◽  
Intestinal Regeneration ◽  
Negative Effect ◽  
Altered Cell ◽  
Holothuria Glaberrima ◽  
Mtt Assays

The increased antibiotics usage in biomedical and agricultural settings has been well documented. Antibiotics have now been shown to exert effects outside their purposive use, including effects on physiological and developmental processes. We explored the effect of various antibiotics on intestinal regeneration in the sea cucumber Holothuria glaberrima. For this, holothurians were eviscerated and left to regenerate for 10 days in seawater with different penicillin/streptomycin-based cocktails (100 µg/mL PS) including: 100 µg/mL kanamycin (KPS), 5 µg/mL vancomycin (VPS), and 4 µg/mL (E4PS) or 20 µg/mL (E20PS) erythromycin. Immunohistological and histochemical analyses were performed to analyze regenerative processes, including rudiment size, extracellular matrix (ECM) remodeling, cell proliferation, and muscle dedifferentiation. A reduction in muscle dedifferentiation was observed in all antibiotic-treated animals. ECM remodeling was decreased by VPS, E4PS, and E20PS treatments. In addition, organisms subjected to E20PS displayed a significant reduction in the size of their regenerating rudiments while VPS exposure altered cell proliferation. MTT assays were used to discard the possibility that the antibiotics directly affect holothurian metabolic activity while bacterial cultures were used to test antibiotic effects on holothurian enteric microbiota. Our results demonstrate a negative effect on intestinal regeneration and strongly suggest that these effects are due to alterations in the microbial community.

scholarly journals Characterization of proteolytic activities during intestinal regeneration of the sea cucumber, Holothuria glaberrima

2012 ◽  
Vol 56 (9) ◽  
pp. 681-691 ◽  
Author(s):  
Consuelo Pasten ◽  
Rey Rosa ◽  
Stephanie Ortiz ◽  
Sebastián González ◽  
José E. García-Arrarás
Keyword(s):  
Sea Cucumber ◽  
Intestinal Regeneration ◽  
Proteolytic Activities ◽  
Holothuria Glaberrima

scholarly journals Retinoic Acid Signaling Is Associated with Cell Proliferation, Muscle Cell Dedifferentiation, and Overall Rudiment Size during Intestinal Regeneration in the Sea Cucumber, Holothuria glaberrima

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 873 ◽  
Author(s):  
Jorge Viera-Vera ◽  
José E. García-Arrarás
Keyword(s):  
Retinoic Acid ◽  
Signaling Pathway ◽  
Retinoic Acid Receptor ◽  
Body Parts ◽  
Cell Dedifferentiation ◽  
Cellular Processes ◽  
Regenerative Response ◽  
Results Of Treatment ◽  
Intestinal Regeneration ◽  
Holothuria Glaberrima

Almost every organism has the ability of repairing damaged tissues or replacing lost and worn out body parts, nevertheless the degree of the response substantially differs between each species. Adult sea cucumbers from the Holothuria glaberrima species can eviscerate various organs and the intestinal system is the first one to regenerate. This process involves the formation of a blastema-like structure that derives from the torn mesentery edges by the intervention of specific cellular processes (e.g., cell dedifferentiation and division). Still, the genetic networks controlling the regenerative response in this model system are just starting to be unraveled. In this work we examined if and how the retinoic acid (RA) signaling pathway is involved in the regenerative response of this deuterostome. We first identified and characterized the holothurian orthologs for short chain dehydrogenase/reductase 7 (SDR7) and aldehyde dehydrogenase family 8A1 (ALDH8A1), two enzymes respectively associated with retinaldehyde and RA anabolism. We then showed that the SDR7 transcript was differentially expressed during specific stages of intestinal regeneration while ALDH8A1 did not show significant differences in regenerating tissues when compared to those of normal (non-eviscerated) organisms. Finally, we investigated the consequences of modulating RA signaling during intestinal regeneration using pharmacological tools. We showed that application of an inhibitor (citral) of the enzyme synthesizing RA or a retinoic acid receptor (RAR) antagonist (LE135) resulted in organisms with a significantly smaller intestinal rudiment when compared to those treated with DMSO (vehicle). The two inhibitors caused a reduction in cell division and cell dedifferentiation in the new regenerate when compared to organisms treated with DMSO. Results of treatment with tazarotene (an RAR agonist) were not significantly different from the control. Taken together, these results suggest that the RA signaling pathway is regulating the cellular processes that are crucial for intestinal regeneration to occur. Thus, RA might be playing a role in echinoderm regeneration that is similar to what has been described in other animal systems.

scholarly journals TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria

2016 ◽  
Vol 473 (2) ◽  
pp. 107-121 ◽  
Author(s):  
Jemma Gatliff ◽  
Michelangelo Campanella
Keyword(s):  
Neurological Diseases ◽  
Anion Channel ◽  
Translocator Protein ◽  
Endocrine Regulation ◽  
Voltage Dependent Anion Channel ◽  
Steroid Synthesis ◽  
Cellular Processes ◽  
Cellular Events ◽  
Voltage Dependent

The 18-kDa translocator protein (TSPO) localizes in the outer mitochondrial membrane (OMM) of cells and is readily up-regulated under various pathological conditions such as cancer, inflammation, mechanical lesions and neurological diseases. Able to bind with high affinity synthetic and endogenous ligands, its core biochemical function resides in the translocation of cholesterol into the mitochondria influencing the subsequent steps of (neuro-)steroid synthesis and systemic endocrine regulation. Over the years, however, TSPO has also been linked to core cellular processes such as apoptosis and autophagy. It interacts and forms complexes with other mitochondrial proteins such as the voltage-dependent anion channel (VDAC) via which signalling and regulatory transduction of these core cellular events may be influenced. Despite nearly 40 years of study, the precise functional role of TSPO beyond cholesterol trafficking remains elusive even though the recent breakthroughs on its high-resolution crystal structure and contribution to quality-control signalling of mitochondria. All this along with a captivating pharmacological profile provides novel opportunities to investigate and understand the significance of this highly conserved protein as well as contribute the development of specific therapeutics as presented and discussed in the present review.

scholarly journals Structural and functional studies of pyruvate carboxylase regulation by cyclic di-AMP in lactic acid bacteria

2017 ◽  
Vol 114 (35) ◽  
pp. E7226-E7235 ◽  
Author(s):  
Philip H. Choi ◽  
Thu Minh Ngoc Vu ◽  
Huong Thi Pham ◽  
Joshua J. Woodward ◽  
Mark S. Turner ◽  
...  
Keyword(s):  
Binding Site ◽  
Conformational Changes ◽  
Pyruvate Carboxylase ◽  
Adenosine Monophosphate ◽  
Binding Mode ◽  
Functional Studies ◽  
Cellular Processes ◽  
Wide Range ◽  
A Site ◽  
Amp Inhibition

Cyclic di-3′,5′-adenosine monophosphate (c-di-AMP) is a broadly conserved bacterial second messenger that has been implicated in a wide range of cellular processes. Our earlier studies showed that c-di-AMP regulates central metabolism inListeria monocytogenesby inhibiting its pyruvate carboxylase (LmPC), a biotin-dependent enzyme with biotin carboxylase (BC) and carboxyltransferase (CT) activities. We report here structural, biochemical, and functional studies on the inhibition ofLactococcus lactisPC (LlPC) by c-di-AMP. The compound is bound at the dimer interface of the CT domain, at a site equivalent to that in LmPC, although it has a distinct binding mode in the LlPC complex. This binding site is not well conserved among PCs, and only a subset of these bacterial enzymes are sensitive to c-di-AMP. Conformational changes in the CT dimer induced by c-di-AMP binding may be the molecular mechanism for its inhibitory activity. Mutations of residues in the binding site can abolish c-di-AMP inhibition. InL. lactis, LlPC is required for efficient milk acidification through its essential role in aspartate biosynthesis. The aspartate pool inL. lactisis negatively regulated by c-di-AMP, and high aspartate levels can be restored by expression of a c-di-AMP–insensitive LlPC. LlPC has high intrinsic catalytic activity and is not sensitive to acetyl-CoA activation, in contrast to other PC enzymes.

scholarly journals Major cellular events in peripheral nerve regeneration: A brief overview

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Naidu M ◽  
David P
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Wallerian Degeneration ◽  
Peripheral Nerve Regeneration ◽  
Scar Tissue ◽  
Regenerative Process ◽  
Cellular Events ◽  
Neural Cell Adhesion ◽  
Proximal Stump ◽  
Regeneration Response

Injury to a peripheral nerve leads to degeneration of the segment distal to the site of lesion, a process referred to as Wallerian degeneration. During Wallerian degeneration, axons and myelin sheaths undergo degeneration and are phagocytosed by macrophages and Schwann cells. The Schwann cells proliferate and the endoneurial tubes persist, together the whole structure is known as the band of Büngner. Within few hours, the damaged axons in the proximal stump initiate a regeneration response, with formation of new growth cones. During Wallerian degeneration, neurotrophins, neural cell adhesion molecules, cytokines and other soluble factors are upregulated to facilitate regeneration. The recovery of the target in mammals is often variable, but almost never complete. In humans, scar tissue forms at the site of lesion and this often results in poor recovery of the target. The major events underlying this regenerative process is highlighted and discussed in this review.

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