Epithelial to Mesenchymal Transition in Human Skin Wound Healing Is Induced by Tumor Necrosis Factor-α through Bone Morphogenic Protein-2

Yan, Chunli; Grimm, Wesley A; Garner, W.L.; Lan, Qing; Travis, Taryn E; Tan, Neiman; Han, Yuan‐Ping

doi:10.2353/ajpath.2010.090048

Cited by 238 publications

(200 citation statements)

References 30 publications

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“…Wound healing in skin has been studied extensively, and several critical molecular processes, such as an inflammatory response, EMT, and ECM remodeling, have been identified (20,21). Similar injury-healing processes were also observed in the heart tissues of our PTSD mouse model.…”

Section: Discussionsupporting

confidence: 54%

Molecular evidence of stress-induced acute heart injury in a mouse model simulating posttraumatic stress disorder

Cho

Lee

Hammamieh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Posttraumatic stress disorder (PTSD) is a common condition induced by life-threatening stress, such as that experienced by soldiers under battlefield conditions. Other than the commonly recognized behavioral and psychological dysfunction, epidemiological studies have also revealed that PTSD patients have a higher risk of other diseases, such as cardiovascular disorders. Using a PTSD mouse model, we investigated the longitudinal transcriptomic changes in heart tissues after the exposure to stress through intimidation. Our results revealed acute heart injury associated with the traumatic experience, reflecting the underlying biological injury processes of the immune response, extracellular matrix remodeling, epithelial-to-mesenchymal cell transitions, and cell proliferation. Whether this type of injury has any longterm effects on heart function is yet to be determined. The differing responses to stress leading to acute heart injury in different inbred strains of mice also suggest that this response has a genetic as well as an environmental component. Accordingly, the results from this study suggest a molecular basis for the observed higher risk of cardiovascular disorders in PTSD patients, which raises the likelihood of cardiac dysfunction induced by long-term stress exposures.systems biology | transcriptome | microRNA

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Section: Discussionsupporting

confidence: 54%

Molecular evidence of stress-induced acute heart injury in a mouse model simulating posttraumatic stress disorder

Cho

Lee

Hammamieh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…This has recently been reported in human skin wound healing. A study using human skin tissues from acute wounds in the phase of re-epithelialisation found that migrating epithelial cells in wound margins and deep epithelial ridges gained mesenchymal features such as vimentin and FSP1 expression [2]. In vitro, tumour necrosis factor-α (TNF-α) induced expression of vimentin, FSP1, and matrix metalloproteinases in normal human skin and primary keratinocytes and this was inhibited by BMP antagonists, suggesting that BMP mediates the TNF-α-induced EMT in human skin.…”

Section: Bmp Emt and Tissue Regenerationmentioning

confidence: 99%

“…It is well known that periods of EMT are necessary during development but can also occur during fibrosis and tumour progression. More recently, EMT-like processes have been described during tissue repair [2,3].…”

Section: Introductionmentioning

confidence: 99%

Regulation of epithelial to mesenchymal transition by bone morphogenetic proteins

McCormack

O’Dea

2013

Cellular Signalling

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“…The autocrine/paracrine signaling of cytokines, such as EGF, TGF-␤, and TNF-␣, regulate EMT morphologic phases in keratinocytes (18,28,29). EGF family members are primary growth factors involved in re-epithelialization during cutaneous wound healing (30,31).…”

Section: Aberrant Glycosylation Of Egf-r Enhances Its Signaling In Gnmentioning

confidence: 99%

“…In adults, EMT, which is driven by the cytokine bath generated by tissue injury, mediates the production of fibroblasts during inflammation and wound healing (18 -20). Re-epithelialization in wound healing involves the motility or migration of epithelial cells, and the migrating epithelial cells in wound margins acquire mesenchymal features and follow early stages of EMT (18).…”

mentioning

confidence: 99%

Enhanced Epithelial-Mesenchymal Transition-like Phenotype in N-Acetylglucosaminyltransferase V Transgenic Mouse Skin Promotes Wound Healing

Terao

Ishikawa

Nakahara

et al. 2011

Journal of Biological Chemistry

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N-Acetylglucosaminyltransferase V (GnT-V) catalyzes the ␤1,6 branching of N-acetylglucosamine on N-glycans. GnT-V expression is elevated during malignant transformation in various types of cancer. However, the mechanism by which GnT-V promotes cancer progression is unclear. To characterize the biological significance of GnT-V, we established GnT-V transgenic (Tg) mice, in which GnT-V is regulated by a ␤-actin promoter. No spontaneous cancer was detected in any organs of the GnT-V Tg mice. However, GnT-V expression was up-regulated in GnT-V Tg mouse skin, and cultured keratinocytes derived from these mice showed enhanced migration, which was associated with changes in E-cadherin localization and epithelial-mesenchymal transition (EMT). Further, EMT-associated factors snail, twist, and N-cadherin were up-regulated, and cutaneous wound healing was accelerated in vivo. We further investigated the detailed mechanisms of EMT by assessing EGF signaling and found up-regulated EGF receptor signaling in GnT-V Tg mouse keratinocytes. These findings indicate that GnT-V overexpression promotes EMT and keratinocyte migration in part through enhanced EGF receptor signaling.Oligosaccharide structure changes are detected following birth, differentiation, and carcinogenesis (1), and these changes are regulated by glycosyltransferases. In particular, N-acetylglucosaminyltransferase V (GnT-V) 3 plays an important role in carcinogenesis and tumor metastasis (2). To characterize the detailed molecular mechanisms underlying GnT-V-related tumor metastasis, we and other groups succeeded in purifying and cloning . In addition, we developed a sugar remodeling system of cancer cells and demonstrated the biological function of GnT-V in tumor metastasis through biochemical analysis of its target glycoproteins (6). Granovsky et al. (7) reported that mammary tumor growth and metastases induced by the polyomavirus middle T oncogene were considerably less in GnT-V-deficient mice than in littermate control mice. Cancer cells established from GnT-V-deficient mice showed lower cell growth and intracellular signaling than control mice because of aberrant glycosylation of growth factor receptors (8). Dennis et al. (9) also reported that sugar metabolism is critical to control the formation of ␤1,6 N-acetylglucosamine (GlcNAc), a product of GnT-V. In contrast, GnT-V is involved in negative regulation of T cell activation, leading to suppression of the autoimmune reaction (10). Recently, Mkhikian et al. (11) reported that genetic changes in glycosylation status for suppressing N-glycan branching are concerned with the incidence of multiple sclerosis. Our groups have studied biological functions of adhesion molecules such as cadherin and integrins in terms of N-glycan branching mediated by GnT-V and have found that GnT-V inhibits cell-cell/cell-matrix adhesion and promotes migration of cancer cells (12).Although GnT-V is known to be up-regulated in the early phase of carcinogenesis in many cancers (13), it is unclear whether GnT-V regulates the late ph...

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Epithelial to Mesenchymal Transition in Human Skin Wound Healing Is Induced by Tumor Necrosis Factor-α through Bone Morphogenic Protein-2

Cited by 238 publications

References 30 publications

Molecular evidence of stress-induced acute heart injury in a mouse model simulating posttraumatic stress disorder

Molecular evidence of stress-induced acute heart injury in a mouse model simulating posttraumatic stress disorder

Regulation of epithelial to mesenchymal transition by bone morphogenetic proteins

Enhanced Epithelial-Mesenchymal Transition-like Phenotype in N-Acetylglucosaminyltransferase V Transgenic Mouse Skin Promotes Wound Healing

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