The MicroRNA miR-199a-5p Down-regulation Switches on Wound Angiogenesis by Derepressing the v-ets Erythroblastosis Virus E26 Oncogene Homolog 1-Matrix Metalloproteinase-1 Pathway

Chan, Yuk Cheung; Roy, Sashwati; Huang, Yanfang; Khanna, Savita; Sen, Chandan K.

doi:10.1074/jbc.m112.413294

Cited by 71 publications

(51 citation statements)

References 56 publications

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“…Downregulation of MiR-199a-5p induces wound angiogenesis by derepressing the MMP-1 expression through the transcription factor V-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1). 65 MiR 29b is a known regulator of TGF-b-mediated fibrosis. Delivery of MiR-29b through a collagen scaffold to full-thickness wounds in vivo reduced wound contraction, improved the ratio of collagen type III/I, and increased the ratio of MMP-8:TIMP-1 resulting in improved ECM remodeling 66 showing the potential of MiR therapy in wound healing (Fig.…”

Section: Mir Regulation Of Mmpsmentioning

confidence: 99%

Metalloproteinases and Wound Healing

Caley¹,

Martins²,

O’Toole³

2015

Advances in Wound Care

614

452

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Significance: Matrix metalloproteinases (MMPs) are present in both acute and chronic wounds. They play a pivotal role, with their inhibitors, in regulating extracellular matrix degradation and deposition that is essential for wound reepithelialization. The excess protease activity can lead to a chronic nonhealing wound. The timed expression and activation of MMPs in response to wounding are vital for successful wound healing. MMPs are grouped into eight families and display extensive homology within these families. This homology leads in part to the initial failure of MMP inhibitors in clinical trials and the development of alternative methods for modulating the MMP activity. MMP-knockout mouse models display altered wound healing responses, but these are often subtle phenotypic changes indicating the overlapping MMP substrate specificity and inter-MMP compensation. Recent Advances: Recent research has identified several new MMP modulators, including photodynamic therapy, protease-absorbing dressing, microRNA regulation, signaling molecules, and peptides. Critical Issues: Wound healing requires the controlled activity of MMPs at all stages of the wound healing process. The loss of MMP regulation is a characteristic of chronic wounds and contributes to the failure to heal. Future Directions: Further research into how MMPs are regulated should allow the development of novel treatments for wound healing. SCOPE AND SIGNIFICANCEThis review highlights recent advances in understanding the regulation of matrix metalloproteinases (MMPs) in skin and how this knowledge might be applied in patients to improve wound healing. Selected recent advances include microRNA (MiR) regulation, novel peptides, signal transduction, experimental therapies, and novel dressings. TRANSLATIONAL RELEVANCEWound healing is a complex multicellular process involving fibroblasts, keratinocytes, and endothelial cells as well as inflammatory cells. The healing process follows an orderly sequence of events incorporating four distinct, yet overlapping, phases: hemostasis, the inflammatory phase, the proliferation phase, and the remodeling phase. The phases of wound healing are regulated by cross talk between different groups of molecules, including extracellular matrix (ECM), integrins, growth factors, and MMPs. Migration of cells on ECM, and remodeling and degradation of the ECM by MMPs are key elements of wound repair. CLINICAL RELEVANCEChronic wounds, including pressure sores, venous ulcers, and diabetic ulcers, are a major clinical problem with considerable morbidity and associated financial costs. Excessive MMPs are a feature of chronic wounds. Regulation of MMP levels in wounds could lead to improved wound healing. OVERVIEWThe MMP family is a group of calcium-dependent zinc-containing enzymes that are involved in the degradation of ECM. Family members share structural ( Fig. 1) and sequence similarities, a flexible proline-rich hinge region, and a hemopexinlike C-terminal domain, which functions in recognition of substrates (usually ECM). Excep...

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Section: Mir Regulation Of Mmpsmentioning

confidence: 99%

Metalloproteinases and Wound Healing

Caley¹,

Martins²,

O’Toole³

2015

Advances in Wound Care

614

452

View full text Add to dashboard Cite

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“…During normoxia, Hif1α is targeted by miR-199a, while, during hypoxia, miR-199a is downregulated (by a still undefined post-transcriptional mechanism), thus contributing to the expression of Hif1α [133]. The therapeutic knockdown of miR-199a during normoxia might therefore be used to mirror hypoxic preconditioning and protect cardiomyocytes against subsequent hypoxic damage, as suggested by recent results [134].…”

Section: Future Directions For Therapy Mir-diagnosis and Mir-drugsmentioning

confidence: 82%

MicroRNAs in myocardial ischemia: identifying new targets and tools for treating heart disease. New frontiers for miR-medicine

Sala

Bergerone

Gatti

et al. 2013

Cell. Mol. Life Sci.

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“…Additionally, miR-199a-5p negatively regulates angiogenic responses by directly targeting v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1). us, downregulation of miR-199a-5p is involved in the induction of wound angiogenesis through derepressing of the Ets-1-MMP1 pathway [102]. is suggests that miR-199a is a regulator of a hypoxia-triggered pathway but also involved in preconditioning of cells against hypoxic damage.…”

Section: Mirnas In Angiogenesismentioning

confidence: 99%

MicroRNAs in Cardiovascular Regenerative Medicine: Directing Tissue Repair and Cellular Differentiation

Sluijter

2013

ISRN Vascular Medicine

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MicroRNAs (miRNAs) are a class of short noncoding RNA molecules, approximately 22 nucleotides in length, which regulate gene expression through inhibition of the translation of target genes. It is now generally accepted that miRNAs guide processes and cellular functions through precise titration of gene dosage, not only for a single gene but also controlling the levels of a large cohort of gene products. miRNA expression is altered in cardiovascular disease and may thereby limit and impair cardiovascular repair responses. Increasing evidence of the essential role of miRNAs in the self-renewal and differentiation of stem cells suggests the opportunity of using the modulation of miRNA levels or their function in directing cell transplantation, cell behavior, and thereby organ healing. In this paper, an overview of miRNA biogenesis and their way of action and different roles that miRNAs play during the myocardial responses to injury and upon cell transplantation will be provided. We focused on cardiomyocyte survival, angiogenesis, extracellular matrix production, and how miRNAs can direct cell plasticity of injected cells and thus drive differentiation for cardiovascular phenotypes, including vascular differentiation and cardiomyocyte differentiation.

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The MicroRNA miR-199a-5p Down-regulation Switches on Wound Angiogenesis by Derepressing the v-ets Erythroblastosis Virus E26 Oncogene Homolog 1-Matrix Metalloproteinase-1 Pathway

Cited by 71 publications

References 56 publications

Metalloproteinases and Wound Healing

Metalloproteinases and Wound Healing

MicroRNAs in myocardial ischemia: identifying new targets and tools for treating heart disease. New frontiers for miR-medicine

MicroRNAs in Cardiovascular Regenerative Medicine: Directing Tissue Repair and Cellular Differentiation

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