BMP-1/tolloid-like proteinases synchronize matrix assembly with growth factor activation to promote morphogenesis and tissue remodeling

Goff, Sandrine Vadon-Le; Hulmes, David J.S.; Moali, Catherine

doi:10.1016/j.matbio.2015.02.006

Cited by 117 publications

(71 citation statements)

References 109 publications

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“…Of note was the Smad4 effector gene which did show induction of expression, an observation that is in line with recent work on Hydra head regeneration [68]. Interestingly, the Tolloid gene ( Nve-Tld [81]), which encodes for an Astacin type metalloproteinase that has multiple substrates including the BMP2/4 antagonist Chordin [82], showed a shift in expression from high oral to aboral with time. However, when we examined BMP antagonist like genes, we found that while Chordin and Noggin orthologs had very low time course responses, kielin/chordin-like (KCP) [83], a gene whose product enhances BMP signaling, displayed high aboral expression.…”

Section: Resultssupporting

confidence: 67%

A transcriptional time-course analysis of oral vs. aboral whole-body regeneration in the Sea anemone Nematostella vectensis

et al. 2016

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BackgroundThe ability of regeneration is essential for the homeostasis of all animals as it allows the repair and renewal of tissues and body parts upon normal turnover or injury. The extent of this ability varies greatly in different animals with the sea anemone Nematostella vectensis, a basal cnidarian model animal, displaying remarkable whole-body regeneration competence.ResultsIn order to study this process in Nematostella we performed an RNA-Seq screen wherein we analyzed and compared the transcriptional response to bisection in the wound-proximal body parts undergoing oral (head) or aboral (tail) regeneration at several time points up to the initial restoration of the basic body shape. The transcriptional profiles of regeneration responsive genes were analyzed so as to define the temporal pattern of differential gene expression associated with the tissue-specific oral and aboral regeneration. The identified genes were characterized according to their GO (gene ontology) assignations revealing groups that were enriched in the regeneration process with particular attention to their affiliation to the major developmental signaling pathways. While some of the genes and gene groups thus analyzed were previously known to be active in regeneration, we have also revealed novel and surprising candidate genes such as cilia-associated genes that likely participate in this important developmental program.ConclusionsThis work highlighted the main groups of genes which showed polarization upon regeneration, notably the proteinases, multiple transcription factors and the Wnt pathway genes that were highly represented, all displaying an intricate temporal balance between the two sides. In addition, the evolutionary comparison performed between regeneration in different animal model systems may reveal the basic mechanisms playing a role in this fascinating process.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3027-1) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 67%

A transcriptional time-course analysis of oral vs. aboral whole-body regeneration in the Sea anemone Nematostella vectensis

et al. 2016

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“…Their experiment confirmed BMP1-like proteinases as essential proteins to the structure and wound healing of the skin. BMP1 proteinases are crucial for the formation of ECM not only by direct influence to its formation but also indirectly by activating TGF-β superfamily members including BMP-2 and BMP-4, profibrotic TGF-β1, and growth and differentiation factors GDF-8/-11 and IGF (24, 26). To date, there are seven different isoforms of the BMP1 protein (25).…”

Section: The Critical Role Of Myofibroblasts and Other Ecm Componentsmentioning

confidence: 99%

Current Therapeutic Approach to Hypertrophic Scars

et al. 2017

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Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome.

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“…Such processing is involved in producing mature collagen monomers capable of assembling into fibrils. Subsequently, studies have expanded the list of proposed BTP substrates to include additional ECM-related proteins biosynthetically processed to their mature/functional forms [1, 3, 4]. These include lysyl oxidase, an enzyme necessary for covalent crosslinking of elastin and collagen fibrils [5]; collagens V and XI, and the small leucine-rich proteoglycans (SLRPs) decorin and biglycan [6-9], all of which play roles in regulating collagen fibrillogenesis [10] [11-13].…”

Section: Introductionmentioning

confidence: 99%

BMP1-like proteinases are essential to the structure and wound healing of skin

et al. 2016

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Closely related extracellular metalloproteinases bone morphogenetic protein 1 (BMP1) and mammalian Tolloid-like 1 (mTLL1) are co-expressed in various tissues and have been suggested to have overlapping roles in the biosynthetic processing of extracellular matrix components. Early lethality of mice null for the BMP1 gene Bmp1 or the mTLL1 gene Tll1 has impaired in vivo studies of these proteinases. To overcome issues of early lethality and functional redundancy we developed the novel BTKO mouse strain, with floxed Bmp1 and Tll1 alleles, for induction of postnatal, simultaneous ablation of the two genes. We previously showed these mice to have a skeletal phenotype that includes elements of osteogenesis imperfecta (OI), osteomalacia, and deficient osteocyte maturation, observations validated by the finding of BMP1 mutations in a subset of human patients with OI-like phenotypes. However, the roles of BMP1-like proteinase in non-skeletal tissues have yet to be explored, despite the supposed importance of putative substrates of these proteinases in such tissues. Here, we employ BTKO mice to investigate potential roles for these proteinases in skin. Loss of BMP1-like proteinase activity is shown to result in markedly thinned and fragile skin with unusually densely packed collagen fibrils and delayed wound healing. We demonstrate deficits in the processing of collagens I and III, decorin, biglycan, and laminin 332 in skin, which indicate mechanisms whereby BMP1-like proteinases affect the biology of this tissue. In contrast, lack of effects on collagen VII processing or deposition indicates this putative substrate to be biosynthetically processed by non-BMP1-like proteinases.

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BMP-1/tolloid-like proteinases synchronize matrix assembly with growth factor activation to promote morphogenesis and tissue remodeling

Cited by 117 publications

References 109 publications

A transcriptional time-course analysis of oral vs. aboral whole-body regeneration in the Sea anemone Nematostella vectensis

A transcriptional time-course analysis of oral vs. aboral whole-body regeneration in the Sea anemone Nematostella vectensis

Current Therapeutic Approach to Hypertrophic Scars

BMP1-like proteinases are essential to the structure and wound healing of skin

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