Changing intracellular compartmentalization of β‐galactosidase in the ROSA26 reporter mouse during embryonic development: A light‐ and electron‐microscopic study

Aoyama, Naoyoshi; Molin, Daniël; Mentink, M. M. T.; Koerten, Henk K.; Ruiter, Marijke; Groot, Adriana C. Gittenberger‐de; Poelmann, Robert E.

doi:10.1002/ar.a.20060

Cited by 4 publications

(2 citation statements)

References 27 publications

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“…AGEs can induce Smad2 phosphorylation in vitro and in vivo ( 26 ), and therefore CML might be responsible for the raise in phosphorylated Smad2. However, VEGF has been reported to inhibit Smad2 phosphorylation ( 48 ); therefore, a reduced level of VEGF in these structures could also relate to the identified increase in Smad2 phosphorylation. Although endothelial to mesenchymal transformation can be increased by TGFβ/Smad2 signaling ( 49 , 50 ), the hypoplastic appearance of the outflow cushions contradicts this assumption.…”

Section: Discussionmentioning

confidence: 99%

Specific Local Cardiovascular Changes of Nɛ-(Carboxymethyl)lysine, Vascular Endothelial Growth Factor, and Smad2 in the Developing Embryos Coincide With Maternal Diabetes–Induced Congenital Heart Defects

et al. 2009

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OBJECTIVE Embryos exposed to a diabetic environment in utero have an increased risk to develop congenital heart malformations. The mechanism behind the teratogenicity of diabetes still remains enigmatic. Detrimental effects of glycation products in diabetic patients have been well documented. We therefore studied a possible link between glycation products and the development of congenital cardiovascular malformations. Furthermore, we investigated other possible mechanisms involved in this pathogenesis: alterations in the levels of vascular endothelial growth factor (VEGF) or phosphorylated Smad2 (the latter can be induced by both glycation products and VEGF). RESEARCH DESIGN AND METHODS We examined the temporal spatial patterning of the glycation products N ε (carboxymethyl)lysine (CML) and methylglyoxal (MG) adducts, VEGF expression, and phosphorylated Smad2 during cardiovascular development in embryos from normal and diabetic rats. RESULTS Maternal diabetes increased the CML accumulation in the areas susceptible to diabetes-induced congenital heart disease, including the outflow tract of the heart and the aortic arch. No MG adducts could be detected, suggesting that CML is more likely to be indicative for increased oxidative stress than for glycation. An increase of CML in the outflow tract of the heart was accompanied by an increase in phosphorylated Smad2, unrelated to VEGF. VEGF showed a time-specific decrease in the outflow tract of embryos from diabetic dams. CONCLUSIONS From our results, we can conclude that maternal diabetes results in transient and localized alterations in CML, VEGF expression, and Smad2 phosphorylation overlapping with those regions of the developing heart that are most sensitive to diabetes-induced congenital heart disease.

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Section: Discussionmentioning

confidence: 99%

Specific Local Cardiovascular Changes of Nɛ-(Carboxymethyl)lysine, Vascular Endothelial Growth Factor, and Smad2 in the Developing Embryos Coincide With Maternal Diabetes–Induced Congenital Heart Defects

et al. 2009

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“…The procedure described by Aoyama et al 32 was followed. Skin samples were trimmed into 1-mm 3 pieces and fixed in 2% paraformaldehyde and 0.1% glutaraldehyde in 0.1 mol/L sodium cacodylate buffer, pH 7.4, for 1 hour at 4°C.…”

Section: Enzyme Electron Microscopymentioning

confidence: 99%

Delineation of Matriptase Protein Expression by Enzymatic Gene Trapping Suggests Diverging Roles in Barrier Function, Hair Formation, and Squamous Cell Carcinogenesis

List¹,

Szabo²,

Molinolo³

et al. 2006

The American Journal of Pathology

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The membrane serine protease matriptase is required for epidermal barrier function, hair formation, and thymocyte development in mice, and dysregulated matriptase expression causes epidermal squamous cell carcinoma. To elucidate the specific functions of matriptase in normal and aberrant epidermal differentiation, we used enzymatic gene trapping combined with immunohistochemical, ultrastructural, and barrier function assays to delineate the spatiotemporal expression and function of matriptase in mouse keratinized tissue development, homeostasis, and malignant transformation. In the interfollicular epidermis, matriptase expression was restricted to postmitotic transitional layer keratinocytes undergoing terminal differentiation. Matriptase was also expressed in keratinizing oral epithelium, where it was required for oral barrier function, and in thymic epithelium. In all three tissues, matriptase colocalized with profilaggrin. In staged embryos, the onset of epidermal matriptase expression coincided with that of profilaggrin expression and acquisition of the epidermal barrier. In marked contrast to stratifying keritinized epithelium, matripase expression commenced already in undifferentiated and rapidly proliferating profilaggrin-negative matrix cells and displayed hair growth cycle-dependent expression. Exposure of the epidermis to carcinogens led to the gradual appearance of matriptase in a keratin-5-positive proliferative cell compartment during malignant progression. Combined with previous studies, these data suggest that matriptase has diverging functions in the genesis of stratified keratinized epithelium, hair follicles, and squamous cell carcinoma. The epithelial compartment of the skin is composed of a multilayered interfollicular epidermis and a follicular epidermis consisting of hair follicles with associated sebaceous glands.1 During epidermal development and homeostasis, cell proliferation and differentiation are compartmentalized and tightly regulated processes. The interfollicular epidermis undergoes continuous renewal when proliferative cells residing in the basal layer commit to differentiation and move outwards to give rise to the spinous layer, the granular layer, the transitional layer, and the terminally differentiated cornified layer, the stratum corneum.2 The interfollicular epidermis serves a critical function as a first line of defense against the external environment by providing a protective barrier against mechanical, chemical, and biological insults.3 The epidermis also provides a water-impermeable barrier that prevents excessive loss of body fluids, a function that is critical for the survival of all terrestrial vertebrates. The epidermal barrier function resides in the stratum corneum and consists of an interlocking meshwork of flattened terminally differentiated keratinocytes in which the plasma membrane is replaced by a highly cross-linked, insoluble cornified envelope of the corneocytes. The corneocytes are connected by desmosomes and are embedded in a specialized intercorneocyte...

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A Preservation Method Supporting Multipurpose Analysis of Long-stored Samples

Molin

Dam

2006

Cell Preservation Technology

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Changing intracellular compartmentalization of β‐galactosidase in the ROSA26 reporter mouse during embryonic development: A light‐ and electron‐microscopic study

Cited by 4 publications

References 27 publications

Specific Local Cardiovascular Changes of Nɛ-(Carboxymethyl)lysine, Vascular Endothelial Growth Factor, and Smad2 in the Developing Embryos Coincide With Maternal Diabetes–Induced Congenital Heart Defects

Specific Local Cardiovascular Changes of Nɛ-(Carboxymethyl)lysine, Vascular Endothelial Growth Factor, and Smad2 in the Developing Embryos Coincide With Maternal Diabetes–Induced Congenital Heart Defects

Delineation of Matriptase Protein Expression by Enzymatic Gene Trapping Suggests Diverging Roles in Barrier Function, Hair Formation, and Squamous Cell Carcinogenesis

A Preservation Method Supporting Multipurpose Analysis of Long-stored Samples

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