Keratin 8 and 18 expression in mesenchymal progenitor cells of regenerating limbs is associated with cell proliferation and differentiation

Corcoran, Jonathan; Ferretti, Patrizia

doi:10.1002/(sici)1097-0177(199712)210:4<355::aid-aja1>3.0.co;2-f

Cited by 38 publications

(25 citation statements)

References 48 publications

(54 reference statements)

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“…The identified proteins were also found to be directly associated as network partners for various pathways, such as upholding of the structure and architecture of the cells. Our study also validates the association of keratin 8 and 18 expressions for cell proliferation and differentiation in the mesenchymal progenitor cells of regenerating limb (18). It has been shown that the treatment of cultured blastemal cells with K8 and K18 antisense oligonucleotides significantly decreases DNA synthesis and induces differences in cell morphology (18).…”

Section: Discussionsupporting

confidence: 84%

“…Our study also validates the association of keratin 8 and 18 expressions for cell proliferation and differentiation in the mesenchymal progenitor cells of regenerating limb (18). It has been shown that the treatment of cultured blastemal cells with K8 and K18 antisense oligonucleotides significantly decreases DNA synthesis and induces differences in cell morphology (18). The inverse association of keratin 17 imparts a decisive role in regeneration because it is shown that the intermediate filament protein, keratin 17, has been involved in inducing the wounded stratified epithelia for regulation of cell growth (19), promoting epithelial proliferation and tumor growth by polarizing the immune response (20), and inducing tumor angiogenesis (21).…”

Section: Discussionsupporting

confidence: 80%

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Proteomic Analysis of Zebrafish Caudal Fin Regeneration

Saxena

Singh

Lakshmi

et al. 2012

Molecular & Cellular Proteomics

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The epimorphic regeneration of zebrafish caudal fin is rapid and complete. We have analyzed the biomechanism of zebrafish caudal fin regeneration at various time points based on differential proteomics approaches. The spectrum of proteome changes caused by regeneration were analyzed among controls (0 h) and 1, 12, 24, 48, and 72 h postamputation involving quantitative differential proteomics analysis based on two-dimensional gel electrophoresis matrix-assisted laser desorption/ionization and differential in-gel electrophoresis Orbitrap analysis. A total of 96 proteins were found differentially regulated between the control nonregenerating and regenerating tissues of different time points for having at least 1.5-fold changes. 90 proteins were identified as differentially regulated for regeneration based on differential in-gel electrophoresis analysis between the control and regenerating tissues. 35 proteins were characterized for its expression in all of the five regenerating time points against the control samples. The proteins identified and associated with regeneration were found to be directly allied with various molecular, biological, and cellular functions. Based on network pathway analysis, the identified proteome data set for regeneration was majorly associated in maintaining cellular structure and architecture. Also the proteins were found associated for the cytoskeleton remodeling pathway and cellular immune defense mechanism. The major proteins that were found differentially regulated during zebrafish caudal fin regeneration includes keratin and its 10 isoforms, cofilin 2, annexin a1, skeletal ␣1 actin, and structural proteins. Annexin A1 was found to be exclusively undergoing phosphorylation during regeneration. The obtained differential proteome and the direct association of the various proteins might lead to a new understanding of the regeneration mechanism. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.014118, 1-19, 2012.Regeneration is an important mechanism found among most of the animals including humans in various tissues and organs towards growth, regrowth, repair, reproduction, and survival. The biomechanism of regeneration has been widely studied but poorly understood because of its different extents in various animals. Understanding the basic molecular mechanism of regeneration in the wound environment is of high significance, because it can lead to an applied possibility of making nonregenerating to a regenerating system.Tissue regeneration in vertebrates is found with extensive capabilities. Regeneration of limbs in urodele and caudal fin in zebrafish are the most projected regeneration studies among vertebrates. Zebrafish regenerates a wide variety of tissue structures including heart, fin, spinal cord, and optic nerve (1-3) based on the characteristic regeneration mechanism involving epithelialization, mesenchymal disorganization, blastema formation, regenerative outgrowth, and termination.A great number of gene families, counting wnt, hox, fgf, fgfr, and msx genes, were shown to...

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 80%

Proteomic Analysis of Zebrafish Caudal Fin Regeneration

Saxena

Singh

Lakshmi

et al. 2012

Molecular & Cellular Proteomics

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“…Another keratin up-regulated in our study is KRT8, which has been previously shown by Ferretti to be transiently expressed in dedifferentiating mesenchymal cells 3-5 days after amputation in adult newt limbs (Corcoran and Ferretti, 1997). Although KRT8 is well-known to dimerize with KRT18 as part of the cytoskeleton in simple epithelial cells, it has also been found to associate with ANXA1, suggesting a role in modulation of the inflammatory response (Croxtall et al, 1998;Rual et al, 2005).…”

Section: Discussionsupporting

confidence: 55%

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

2009

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During amphibian epimorphic limb regeneration, local injury produces metabolic changes that lead to cellular dedifferentiation and formation of a blastema, but few details of these changes have been elucidated. Here we report the first global proteomic analysis of epimorphic regeneration comparing the profiles of abundant proteins in larval limbs of the anuran Xenopus laevis (stage 53) at the time of amputation (0dPA) and 3 days post-amputation when the regeneration blastema is developing (3dPA). We identified and quantified 1517 peptides, of which 1067 were identified with high peptide ID confidence. Of these 1067 proteins, 489 showed significant changes in quantity between the two groups. Taking into account identical peptides whose fold changes were within 20%, and not including peptides whose fold changes were below the observed fold changes of peptides for the internal standard (chicken lysozyme), we were able to identify 145 peptides elevated in 3dPA relative to 0dPA and 220 peptides in 0dPA relative to 3dPA. In this report, we focus on those proteins that were elevated in the 3dPA tissue relative to 0dPA. In this class were members of the annexin family (e.g. ANXA1, ANXA2, ANXA5) and the ANXA2-binding partner S100A10, which have important immunoregulatory roles in other systems and were also shown to be differentially expressed in stage 53 and 57 3dPA and 5dPA blastemas in our previous microarray studies. Besides elucidating the possible modulation of inflammation during amphibian limb regeneration, our proteomic study also provides insight into dedifferentiation by revealing up-regulation of proteins known to characterize many stem cells.

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“…It is not clear at this stage whether their expression in the amphibian and human spinal cord plays only a structural role or has additional important functions. It has been suggested that in the regenerating amphibian limb their expression may be causally related to differentiation (Corcoran and Ferretti 1997); one could therefore postulate that the progression of radial glia differentiation into ependyma requires down-regulation of these proteins, and that lack of it might play a role in maintaining a more plastic phenotype in urodeles.…”

Section: Resultsmentioning

confidence: 99%

Up-regulation of neural stem cell markers suggests the occurrence of dedifferentiation in regenerating spinal cord

Walder¹,

Zhang²,

Ferretti³

2003

Development Genes and Evolution

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Following tail amputation in urodele amphibians, an ependymal tube, that resembles a developing neural tube, forms from ependymal cells that migrate from the cord stump and elongates by cell proliferation. Expression of the keratin pair 8 and 18 has been observed in the developing urodele nervous system and is maintained in the ependymal cells of the mature cord. We show here that expression of these keratins is not unique to urodeles, but is also observed in the radial glia of the human spinal cord, suggesting that these proteins might play a role both in neural development and regeneration. Analysis of their expression in the regenerating spinal cord following tail amputation shows that their expression, as well as that of glial fibrillary acidic protein (GFAP), is maintained in the ependymal tube during regeneration, though differences in their levels of expression are observed along the anteroposterior axis and appear to be related to the progression of morphogenesis. In addition, we show that following tail amputation the ependymal tube expresses the neural stem cell markers nestin and vimentin, which are undetectable in normal urodele spinal cord. This up-regulation of neural stem cell markers shows that the ependymal cells undergo a phenotypic change. Whereas maintenance of keratin and GFAP expression in the adult ependyma may reflect a higher plasticity of these cells in adult urodeles than in other vertebrates, re-expression of markers of early neural development suggests the occurrence of a dedifferentiation process in the spinal cord in response to injury.

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Keratin 8 and 18 expression in mesenchymal progenitor cells of regenerating limbs is associated with cell proliferation and differentiation

Cited by 38 publications

References 48 publications

Proteomic Analysis of Zebrafish Caudal Fin Regeneration

Proteomic Analysis of Zebrafish Caudal Fin Regeneration

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

Up-regulation of neural stem cell markers suggests the occurrence of dedifferentiation in regenerating spinal cord

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