Macrophages modulate fibrosis during newt lens regeneration

Tsissios, Georgios; Sallese, Anthony; Pérez-Estrada, J. Raúl; Tangeman, Jared Austin; Chen, Wei-Hao; Smucker, Byran J.; Ratvasky, Sophia; Grajales-Esquivel, Erika; Martinez, Arielle; Visser, Koch; Araus, Alberto Joven; Wang, Hui; Simon, András; Yun, Maximina H.; Rio‐Tsonis, Katia Del

doi:10.1101/2023.06.04.543633

Cited by 3 publications

(4 citation statements)

References 141 publications

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“…However, a secondary injury alone or the addition of FGF2 restarted the scar resolution and the regeneration processes. The findings in the study indicate the importance and multiple functions of macrophages in facilitating a pro-regenerative environment in the newt eye, helping to resolve fibrosis, modulating the overall inflammatory landscape, and maintaining the proper balance of early proliferation and late apoptosis between scarring and regenerative phenotypes [188].…”

Section: Role Of Immune System In Nr Regeneration In Amphibiansmentioning

confidence: 79%

“…Recently, a broad study was conducted on the role of macrophages in the regeneration of the lens that occurs through the conversion of iris cells in the newts N. viridescens and P. waltl [188]. The authors of the study generated a transgenic newt reporter line, in which macrophages can be visualized in vivo.…”

Section: Role Of Immune System In Nr Regeneration In Amphibiansmentioning

confidence: 99%

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Cellular and Molecular Triggers of Retinal Regeneration in Amphibians

Markitantova,

Grigoryan

2023

Life

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Understanding the mechanisms triggering the initiation of retinal regeneration in amphibians may advance the quest for prevention and treatment options for degenerating human retina diseases. Natural retinal regeneration in amphibians requires two cell sources, namely retinal pigment epithelium (RPE) and ciliary marginal zone. The disruption of RPE interaction with photoreceptors through surgery or injury triggers local and systemic responses for retinal protection. In mammals, disease-induced damage to the retina results in the shutdown of the function, cellular or oxidative stress, pronounced immune response, cell death and retinal degeneration. In contrast to retinal pathology in mammals, regenerative responses in amphibians have taxon-specific features ensuring efficient regeneration. These include rapid hemostasis, the recruitment of cells and factors of endogenous defense systems, activities of the immature immune system, high cell viability, and the efficiency of the extracellular matrix, cytoskeleton, and cell surface remodeling. These reactions are controlled by specific signaling pathways, transcription factors, and the epigenome, which are insufficiently studied. This review provides a summary of the mechanisms initiating retinal regeneration in amphibians and reveals its features collectively directed at recruiting universal responses to trauma to activate the cell sources of retinal regeneration. This study of the integrated molecular network of these processes is a prospect for future research in demand biomedicine.

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Section: Role Of Immune System In Nr Regeneration In Amphibiansmentioning

confidence: 79%

Section: Role Of Immune System In Nr Regeneration In Amphibiansmentioning

confidence: 99%

Cellular and Molecular Triggers of Retinal Regeneration in Amphibians

Markitantova,

Grigoryan

2023

Life

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“…This is due to the large number of genes from this category (5640) and also to the closeness of the expected and obtained numbers of up-regulated genes in the samples. The binding activity is associated with mRNA binding processes that determine the specificity of the processing, splicing, and translation of mRNA ("early" sample: p-value 1.91 × 10‾ 12 , FDR 9.66 × 10‾ 9 and "late" sample: p-value 9.45 × 10‾ 29 , FDR 4.78 × 10‾ 25 ). The significance of the enrichment of up-regulated genes/proteins of all other classes at the early stage of RPE reprogramming has not been confirmed while taking into account the FDR values.…”

Section: Up-regulated Genes At the Studied Stages Of The Rpe Reprogra...mentioning

confidence: 99%

“…Studies on newt tissue regeneration are making progress thanks to incorporating highly efficient technologies and allowing us to use microquantities of tissue for the analysis of transcriptomes, genomes, and proteomes [23,24], as well as for the analysis of gene functions [25][26][27]. The application of these approaches allow us to unravel the cellular and molecular mechanisms of aging and its relations with regeneration [28,29].…”

Section: Introductionmentioning

confidence: 99%

Molecular Signatures Integral to Natural Reprogramming in the Pigment Epithelium Cells after Retinal Detachment in Pleurodeles waltl

Markitantova,

Fokin,

Boguslavsky

et al. 2023

IJMS

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The reprogramming of retinal pigment epithelium (RPE) cells into retinal cells (transdifferentiation) lies in the bases of retinal regeneration in several Urodela. The identification of the key genes involved in this process helps with looking for approaches to the prevention and treatment of RPE-related degenerative diseases of the human retina. The purpose of our study was to examine the transcriptome changes at initial stages of RPE cell reprogramming in adult newt Pleurodeles waltl. RPE was isolated from the eye samples of day 0, 4, and 7 after experimental surgical detachment of the neural retina and was used for a de novo transcriptome assembly through the RNA-Seq method. A total of 1019 transcripts corresponding to the differently expressed genes have been revealed in silico: the 83 increased the expression at an early stage, and 168 increased the expression at a late stage of RPE reprogramming. We have identified up-regulation of classical early response genes, chaperones and co-chaperones, genes involved in the regulation of protein biosynthesis, suppressors of oncogenes, and EMT-related genes. We revealed the growth in the proportion of down-regulated ribosomal and translation-associated genes. Our findings contribute to revealing the molecular mechanism of RPE reprogramming in Urodela.

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Loss of the ability to regenerate body appendages in vertebrates: from side effects of evolutionary innovations to gene loss

Zaraisky,

Araslanova,

Shitikov

et al. 2024

Biological Reviews

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The ability to regenerate large body appendages is an ancestral trait of vertebrates, which varies across different animal groups. While anamniotes (fish and amphibians) commonly possess this ability, it is notably restricted in amniotes (reptiles, birds, and mammals). In this review, we explore the factors contributing to the loss of regenerative capabilities in amniotes. First, we analyse the potential negative impacts on appendage regeneration caused by four evolutionary innovations: advanced immunity, skin keratinization, whole‐body endothermy, and increased body size. These innovations emerged as amniotes transitioned to terrestrial habitats and were correlated with a decline in regeneration capability. Second, we examine the role played by the loss of regeneration‐related enhancers and genes initiated by these innovations in the fixation of an inability to regenerate body appendages at the genomic level. We propose that following the cessation of regenerative capacity, the loss of highly specific regeneration enhancers could represent an evolutionarily neutral event. Consequently, the loss of such enhancers might promptly follow the suppression of regeneration as a side effect of evolutionary innovations. By contrast, the loss of regeneration‐related genes, due to their pleiotropic functions, would only take place if such loss was accompanied by additional evolutionary innovations that compensated for the loss of pleiotropic functions unrelated to regeneration, which would remain even after participation of these genes in regeneration was lost. Through a review of the literature, we provide evidence that, in many cases, the loss in amniotes of genes associated with body appendage regeneration in anamniotes was significantly delayed relative to the time when regenerative capability was lost. We hypothesise that this delay may be attributed to the necessity for evolutionary restructuring of developmental mechanisms to create conditions where the loss of these genes was a beneficial innovation for the organism. Experimental investigation of the downregulation of genes involved in the regeneration of body appendages in anamniotes but absent in amniotes offers a promising avenue to uncover evolutionary innovations that emerged from the loss of these genes. We propose that the vast majority of regeneration‐related genes lost in amniotes (about 150 in humans) may be involved in regulating the early stages of limb and tail regeneration in anamniotes. Disruption of this stage, rather than the late stage, may not interfere with the mechanisms of limb and tail bud development during embryogenesis, as these mechanisms share similarities with those operating in the late stage of regeneration. Consequently, the most promising approach to restoring regeneration in humans may involve creating analogs of embryonic limb buds using stem cell‐based tissue‐engineering methods, followed by their transfer to the amputation stump. Due to the loss of many genes required specifically during the early stage of regeneration, this approach may be more effective than attempting to induce both early and late stages of regeneration directly in the stump itself.

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Macrophages modulate fibrosis during newt lens regeneration

Cited by 3 publications

References 141 publications

Cellular and Molecular Triggers of Retinal Regeneration in Amphibians

Cellular and Molecular Triggers of Retinal Regeneration in Amphibians

Molecular Signatures Integral to Natural Reprogramming in the Pigment Epithelium Cells after Retinal Detachment in Pleurodeles waltl

Loss of the ability to regenerate body appendages in vertebrates: from side effects of evolutionary innovations to gene loss

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