Structure, expression, and developmental function of early divergent forms of metalloproteinases in Hydra

Sarras, Michael P.; Li, Yan; Leontovich, Alexey A.; Zhang, Jin Song

doi:10.1038/sj.cr.7290123

Cited by 29 publications

(20 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Injury induces the expression of MMPs, and these perform multiple, distinct functions in wound repair, cell migration and bacterial inhibition and killing [106]. MMP-like proteins have been identified in a diverse array of invertebrates [107, 108]. Planarians have four MMP-like genes ( Smed-mmp1, Smed-mmp2, Smed-mt-mmpA and Smed-mt-mmpB ) with roles in proliferation, apoptosis and cell migration [109].…”

Section: The Planarian Innate Immune Systemmentioning

confidence: 99%

Innate immune system and tissue regeneration in planarians: An area ripe for exploration

Peiris

Hoyer

Oviedo

2014

Seminars in Immunology

View full text Add to dashboard Cite

The immune system has been implicated as an important modulator of tissue regeneration. However, the mechanisms driving injury-induced immune response and tissue repair remain poorly understood. For over 200 years, planarians have been a classical model for studies on tissue regeneration, but the planarian immune system and its potential role in repair is largely unknown. We found through comparative genomic analysis and data mining that planarians contain many potential homologs of the innate immune system that are activated during injury and repair of adult tissues. These findings support the notion that the relationship between adult tissue repair and the immune system is an ancient feature of basal Bilateria. Further analysis of the planarian immune system during regeneration could potentially add to our understanding of how the innate immune system and inflammatory responses interplay with regenerative signals to induce scar-less tissue repair in the context of the adult organism.

show abstract

Section: The Planarian Innate Immune Systemmentioning

confidence: 99%

Innate immune system and tissue regeneration in planarians: An area ripe for exploration

Peiris

Hoyer

Oviedo

2014

Seminars in Immunology

View full text Add to dashboard Cite

show abstract

“…Because of the high level of redundancy, mechanistic understanding of their functions in vivo has often been elusive in mammalian models [42], [43]. MMP-like enzymes have been identified in diverse invertebrate groups, including echinoderms, crustaceans, nematodes, and also in organisms as simple as Hydra [44], [45], [46], [47]. Among invertebrates most information comes from Drosophila, whose genome encodes only two MMPs - one secreted type and one membrane-anchored type [48], [49].…”

Section: Introductionmentioning

confidence: 99%

Planarians as a Model to Assess In Vivo the Role of Matrix Metalloproteinase Genes during Homeostasis and Regeneration

et al. 2013

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2) are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB) are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi) during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi). Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues. These results have high potential to generate significant information for development of regenerative and anti cancer therapies.

show abstract

“…Metalloproteinases are highly conserved multifunctional enzymes, involved in morphogenetic as well as digestive processes in cnidarians (Pan et al, 1998;Sarras et al, 2002). In bilaterians, protease inhibitors restrict their activity according to a tight balance that prevents cellular defects as autodigestion (Witt et al, 2000), abnormal cell migration and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Silencing of the hydra serine protease inhibitorKazal1gene mimics the humanSPINK1pancreatic phenotype

Chera

Rosa

Miljkovic‐Licina

et al. 2006

Journal of Cell Science

View full text Add to dashboard Cite

In hydra, the endodermal epithelial cells carry out the digestive function together with the gland cells that produce zymogens and express the evolutionarily conserved gene Kazal1. To assess the hydra Kazal1 function, we silenced gene expression through double-stranded RNA feeding. A progressive Kazal1 silencing affected homeostatic conditions as evidenced by the low budding rate and the induced animal death. Concomitantly, a dramatic disorganization followed by a massive death of gland cells was observed, whereas the cytoplasm of digestive cells became highly vacuolated. The presence of mitochondria and late endosomes within those vacuoles assigned them as autophagosomes. The enhanced Kazal1 expression in regenerating tips was strongly diminished in Kazal1(-) hydra, and the amputation stress led to an immediate disorganization of the gland cells, vacuolization of the digestive cells and death after prolonged silencing. This first cellular phenotype resulting from a gene knock-down in cnidarians suggests that the Kazal1 serine-protease-inhibitor activity is required to prevent excessive autophagy in intact hydra and to exert a cytoprotective function to survive the amputation stress. Interestingly, these functions parallel the pancreatic autophagy phenotype observed upon mutation within the Kazal domain of the SPINK1 and SPINK3 genes in human and mice, respectively

show abstract

Structure, expression, and developmental function of early divergent forms of metalloproteinases in Hydra

Cited by 29 publications

References 80 publications

Innate immune system and tissue regeneration in planarians: An area ripe for exploration

Innate immune system and tissue regeneration in planarians: An area ripe for exploration

Planarians as a Model to Assess In Vivo the Role of Matrix Metalloproteinase Genes during Homeostasis and Regeneration

Silencing of the hydra serine protease inhibitorKazal1gene mimics the humanSPINK1pancreatic phenotype

Contact Info

Product

Resources

About