Expression of the EMILIN-1 gene during mouse development

Braghetta, Paola; Ferrari, Alessandra; Gemmis, Paola de; Zanetti, Miriam; Volpin, Dino; Bonaldo, Paolo; Bressan, Giorgio M.

doi:10.1016/s0945-053x(02)00072-0

Cited by 27 publications

(42 citation statements)

References 17 publications

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“…The expression of the transgenic Emilin1 promoter in embryos reproduced the complexity expected from the distribution of endogenous gene products ( Figure I in the online-only Data Supplement). 1,3,9 Matching of this promoter activity with that of the endogenous gene was investigated in mice harboring the human EMILIN1 cDNA in Emilin1 +/− embryos. As shown in Figure Table).…”

Section: Transgenes Expression Patternsmentioning

confidence: 99%

“…1,2 All 4 proteins are expressed in the cardiovascular system, however, with significant differences concerning their fine distribution. 1,3,4 While Emilin-1 is expressed by endocardium and right ventricle myocytes and by cells of the entire blood vessel wall (endothelial cells [ECs], smooth muscle cells [SMCs] and adventitial fibroblasts), the other genes have a more restricted expression pattern: Emilin2 is active in myocardium, whereas Mmrn1 and Mmrn2 are expressed only by ECs in blood vessels and, in addition, in platelets and endocardial cells, respectively.…”

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confidence: 99%

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Vascular Smooth Muscle Emilin-1 Is a Regulator of Arteriolar Myogenic Response and Blood Pressure

Litteri

Carnevale

D’Urso

et al. 2012

ATVB

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Objective-Emilin-1 is a protein of elastic extracellular matrix involved in blood pressure (BP) control by negatively affecting transforming growth factor (TGF)-β processing. Emilin1 null mice are hypertensive. This study investigates how Emilin-1 deals with vascular mechanisms regulating BP. Methods and Results-This study uses a phenotype rescue approach in which Emilin-1 is expressed in either endothelial cells or vascular smooth muscle cells of transgenic animals with the Emilin1 −/− background. We found that normalization of BP required Emilin-1 expression in smooth muscle cells, whereas expression of the protein in endothelial cells did not modify the hypertensive phenotype of Emilin1 −/− mice. We also explored the effect of treatment with anti-TGF-β antibodies on the hypertensive phenotype of Emilin1 −/− mice, finding that neutralization of TGF-β in Emilin1 null mice normalized BP quite rapidly (2 weeks). Finally, we evaluated the vasoconstriction response of resistance arteries to perfusion pressure and neurohumoral agents in different transgenic mouse lines. Interestingly, we found that the hypertensive phenotype was coupled with an increased arteriolar myogenic response to perfusion pressure, while the vasoconstriction induced by neurohumoral agents remained unaffected. We further elucidate that, as for the hypertensive phenotype, the increased myogenic response was attributable to increased TGF-β activity. Key Words: Emilin1 ◼ myogenic response ◼ systemic hypertension ◼ transforming growth factor ◼ vascular smooth muscle Conclusion-Our

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Section: Transgenes Expression Patternsmentioning

confidence: 99%

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confidence: 99%

Vascular Smooth Muscle Emilin-1 Is a Regulator of Arteriolar Myogenic Response and Blood Pressure

Litteri

Carnevale

D’Urso

et al. 2012

ATVB

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“…Expression of promoter-lacZ constructs was studied mainly on founder embryos at E14.5. Mouse lines were derived with some of the constructs for analysis of transgene expression at different developmental stages, considering that expression of Emilin1 mRNA begins soon after implantation (13).…”

Section: Constructs P(630 -350)-cat P(630 -441)-cat and P(630 -47mentioning

confidence: 99%

“…2) The absence of ectopic expression with the 8.7-lacZ and 8.7-lacZ-intron indicates that the 5Ј-flanking region contains sequences limiting transcription in tissues where Emilin1 is not produced, like embryonic epithelia and central nervous system (13). One of these sequences is likely located within the proximal 169 bp, as deletion of this stretch from the 8.7-kb fragment (construct 8.7⌬-lacZ) gives rise to ectopic expression of the transgene at high frequency.…”

Section: Constructs P(630 -350)-cat P(630 -441)-cat and P(630 -47mentioning

confidence: 99%

“…A function of Emilin1 in elastogenesis is also indicated by the finding that the protein binds to other components of elastic fibers such as Elastin and Fibulin-5 (12). However, analysis of the distribution of Emilin1 mRNA during mouse development induces us to suggest additional functions of Emilin1 not related to elastic fibers; in fact, early after implantation, Emilin1 mRNA is detected not only in the cardiovascular system but also in extra-embryonic tissues (extra-embryonic visceral endoderm, ectoplacental cone, and spongiotrophoblast), epithelial tissues that do not produce elastic fibers (13). During organogenesis high level expression is found in interstitial connective tissue, perichondrium, and mesenchymal condensations, sites containing elastic fibers.…”

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Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

Fabbro

Gemmis

Braghetta

et al. 2005

Journal of Biological Chemistry

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The location of regions that regulate transcription of the murine Emilin1 gene was investigated in a DNA fragment of 16.8 kb, including the entire gene and about 8.7 and 0.6 kb of 5-and 3-flanking sequences, respectively. The 8.7-kb segment contains the 5-end of the putative 2310015E02Rik gene and the sequence that separates it from Emilin1, whereas the 0.6-kb fragment covers the region between Emilin1 and Ketohexokinase genes. Sequence comparison between species identified several conserved regions in the 5-flanking sequence. Most of them contained chromatin DNase I-hypersensitive sites, which were located at about ؊950 (HS1), ؊3100 (HS2), ؊4750 (HS3), and ؊5150 (HS4) in cells expressing Emilin1 mRNA. Emilin1 transcription initiates at multiple sites, the major of which correspond to two Initiator sequences. Promoter assays suggest that core promoter activity was mainly dependent on Initiator1 and on Sp1-binding sites close to the Initiators. Moreover, one important regulatory region was contained between ؊1 and ؊169 bp and a second one between ؊630 bp and ؊1.1 kb. The latter harbors a putative binding site for transcription factor AP1 matching the location of HS1. The function of different regions was studied by expressing lacZ constructs in transgenic mice. The results show that the 16.8-kb segment contains regulatory sequences driving high level transcription in all the tissues where Emilin1 is expressed. Moreover, the data suggest that transcription in different tissues is achieved through combinatorial cooperation between various regions, rather than being dependent on a single cis-activating region specific for each tissue.

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Emilin genes are duplicated and dynamically expressed during zebrafish embryonic development

Milanetto

Tiso

Braghetta

et al. 2007

Developmental Dynamics

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Emilins are a family of extracellular matrix proteins with common structural organization and containing a characteristic N-terminal cysteine-rich domain. The prototype of this family, Emilin-1, is found in human and murine organs in association with elastic fibers, and other emilins were recently isolated in mammals. To gain insight into these proteins in lower vertebrates, we investigated the expression of emilins in the fish Danio rerio. Using sequence similarity tools, we identified eight members of this family in zebrafish. Each emilin gene has two paralogs in zebrafish, showing conserved structure with the human ortholog. In situ hybridization revealed that expression of zebrafish emilin genes is regulated in a spatiotemporal manner during embryonic development, with overlapping and site-specific patterns mostly including mesenchymal structures. Expression of certain emilin genes in peculiar areas, such as the central nervous system or the posterior notochord, suggests that they may play a role in key morphogenetic processes. Developmental Dynamics 237:222-232, 2008.

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Expression of the EMILIN-1 gene during mouse development

Cited by 27 publications

References 17 publications

Vascular Smooth Muscle Emilin-1 Is a Regulator of Arteriolar Myogenic Response and Blood Pressure

Vascular Smooth Muscle Emilin-1 Is a Regulator of Arteriolar Myogenic Response and Blood Pressure

Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

Emilin genes are duplicated and dynamically expressed during zebrafish embryonic development

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