BMP-2 Induces Versican and Hyaluronan That Contribute to Post-EMT AV Cushion Cell Migration

Inai, Kei; Burnside, Jessica L.; Hoffman, Stanley; Toole, Bryan P.; Sugi, Yukiko

doi:10.1371/journal.pone.0077593

Cited by 25 publications

(21 citation statements)

References 58 publications

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“…The mechanism of ROCK inhibitor influence on wound healing may be suggested from experiments with cardiac cells, where ROCK is induced by TGF-β and inhibits bone morphogenetic protein (BMP)-2 expression (Wang et al, 2012b). At the same time BMP-2 can mediate cell migration by inducing some ECM components (Inai et al, 2013). Therefore, ROCK inhibition may switch signaling from profibrotic TGF-β to pro-migratory BMP, and thus promote cell migration necessary for wound healing.…”

Section: Corneal Epithelial Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

644

554

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Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.

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Section: Corneal Epithelial Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

644

554

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“…Endocardial cushions, beginning as acellular cardiac jelly, will develop in the AV canal as well as in the OFT. The cardiac jelly, sometimes considered the myocardial basement membrane, contains extracellular matrix components such as hyaluronan and aggrecan and will become cellularized by endocardial‐mesenchymal transition (EMT) primarily from the overlying endocardium . Secondarily, other cell populations take part in expanding the cushions.…”

Section: The Oft Endocardial Cushionsmentioning

confidence: 99%

Development and evolution of the metazoan heart

Poelmann

Groot

2019

Developmental Dynamics

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The mechanisms of the evolution and development of the heart in metazoans are highlighted, starting with the evolutionary origin of the contractile cell, supposedly the precursor of cardiomyocytes. The last eukaryotic common ancestor is likely a combination of several cellular organisms containing their specific metabolic pathways and genetic signaling networks. During evolution, these tool kits diversified. Shared parts of these conserved tool kits act in the development and functioning of pumping hearts and open or closed circulations in such diverse species as arthropods, mollusks, and chordates. The genetic tool kits became more complex by gene duplications, addition of epigenetic modifications, influence of environmental factors, incorporation of viral genomes, cardiac changes necessitated by air‐breathing, and many others. We evaluate mechanisms involved in mollusks in the formation of three separate hearts and in arthropods in the formation of a tubular heart. A tubular heart is also present in embryonic stages of chordates, providing the septated four‐chambered heart, in birds and mammals passing through stages with first and second heart fields. The four‐chambered heart permits the formation of high‐pressure systemic and low‐pressure pulmonary circulation in birds and mammals, allowing for high metabolic rates and maintenance of body temperature. Crocodiles also have a (nearly) separated circulation, but their resting temperature conforms with the environment. We argue that endothermic ancestors lost the capacity to elevate their body temperature during evolution, resulting in ectothermic modern crocodilians. Finally, a clinically relevant paragraph reviews the occurrence of congenital cardiac malformations in humans as derailments of signaling pathways during embryonic development.

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“…Bmp2 has been shown to be important for promoting expression of proteoglycans, including versican and hyaluronan, in the remodeling valves. 41 In addition, Sox9 and Scleraxis regulate expression of other ECM components associated with the fibrosa and spongiosa layers, respectively. In mice, Sox9 is required during the remodeling stages for expression of known cartilaginous downstream target genes Col2a1 and Cartilage Link Protein within the leaflets.…”

Section: Contribution Of Non-endothelial Cell Lineages To Valve Strucmentioning

confidence: 99%