Alternative Splicing and Tissue-specific Elastin Misassembly Act as Biological Modifiers of Human Elastin Gene Frameshift Mutations Associated with Dominant Cutis Laxa

Sugitani, Hideki; Hirano, Eiichi; Knutsen, Russell H.; Shifren, Adrián; Wagenseil, Jessica E.; Ciliberto, Christopher; Kozel, Beth A.; Urban, Zsolt; Davis, Elaine C.; Broekelmann, Thomas J.; Mecham, Robert P.

doi:10.1074/jbc.m111.327940

Cited by 32 publications

(40 citation statements)

References 51 publications

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“…Synthesized by fibroblasts and keratinocytes, elastin provides support to the blood vessels, lungs and skin [30,37,38].…”

Section: Elastin Fibre Generation and Architecturementioning

confidence: 99%

“…Unlike other proteins, a single gene known as ELN, which is localized on chromosome 7 and expressed by different cell types throughout development, codes for elastin in humans [38,59,60]. As a result of alternative splicing, different isoforms of the soluble tropoelastin protein have previously been identified, suggesting a potential regulatory mechanism in the expression of this gene.…”

Section: Elastin and Alternative Splicingmentioning

confidence: 99%

“…As a result of alternative splicing, different isoforms of the soluble tropoelastin protein have previously been identified, suggesting a potential regulatory mechanism in the expression of this gene. It is known that different tropoelastin isoforms may affect the physical properties of fibres due to changes in the domains in which crosslinking should occur [37,38,61].…”

Section: Elastin and Alternative Splicingmentioning

confidence: 99%

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Elastin structure and its involvement in skin photoageing

Weihermann

Lorencini

Brohem

et al. 2016

Intern J of Cosmetic Sci

148

102

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Skin aging is a complex process that may be caused by factors that are intrinsic and extrinsic to the body. Ultraviolet (UV) radiation represents one of the main sources of skin damage over the years and characterizes a process known as photoaging. Among the changes that affect cutaneous tissue with age, the loss of elastic properties caused by changes in elastin production, increased degradation and/or processing produces a substantial impact on tissue esthetics and health. The occurrence of solar elastosis is one of the main markers of cutaneous photoaging and is characterized by disorganized and non-functional deposition of elastic fibers. The occurrence of UV radiation-induced alternative splicing of the elastin gene, which leads to inadequate synthesis of the proteins required for the correct assembly of elastic fibers, is a potential explanation for this phenomenon. Innovative studies have been fundamental for the elucidation of rarely explored photoaging mechanisms and have enabled the identification of effective therapeutic alternatives such as cosmetic products. This review addresses cutaneous photoaging and the changes that affect elastin in this process.R esum e Le vieillissement de la peau est un processus complexe qui peutêtre caus e par des facteurs intrins eques et extrins eques du corps. Les rayons ultraviolets (UV) repr esentent l'une des principales sources de dommages de la peau au fil des ans et caract erise un processus connu sous le nom de photo-vieillissement. Parmi les changements qui affectent le tissu cutan e avec l'âge, la perte des propri et es elastiques caus ees par des changements dans la production d' elastine, augmentation de la d egradation et / ou le traitement, produit un impact important sur l'esth etique et la sant e des tissus. La survenue d'une elastose solaire est l'un des principaux marqueurs de photo-vieillissement cutan e et se caract erise par un d epôt d esordonn e et non-fonctionnel des fibres elastiques. L'apparition d'un epissage alternatif du g ene de l' elastine induit par le rayonnement UV, ce qui conduit a une synth ese insuffisante des prot eines n ecessaires a l'assemblage correct des fibres elastiques, est une explication possible de ce ph enom ene. Des etudes novatrices ont et e fondamentales pour l' elucidation des m ecanismes de photovieillissement rarement explor es et ont permis l'identification d'alternatives th erapeutiques efficaces, tels que les produits cosm etiques. Cette revue porte sur le photo-vieillissement cutan e et les changements qui affectent l' elastine dans ce processus.

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“…Synthesized by fibroblasts and keratinocytes, elastin provides support to the blood vessels, lungs and skin [30,37,38].…”

Section: Elastin Fibre Generation and Architecturementioning

confidence: 99%

Section: Elastin and Alternative Splicingmentioning

confidence: 99%

Section: Elastin and Alternative Splicingmentioning

confidence: 99%

See 1 more Smart Citation

Elastin structure and its involvement in skin photoageing

Weihermann

Lorencini

Brohem

et al. 2016

Intern J of Cosmetic Sci

148

102

View full text Add to dashboard Cite

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“…6) and autosomal dominant cutis laxa (ADCL) caused by elastin mutations (Ref. 7). Mutations in accessory glycoproteins such as fibulins-4 or -5 cause autosomal recessive cutis laxa (ARCL) (Ref.…”

Section: Teleosteimentioning

confidence: 99%

Elastic fibres in health and disease

Baldwin

Simpson

Steer

et al. 2013

Expert Rev. Mol. Med.

243

158

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Elastic fibres are insoluble components of the extracellular matrix of dynamic connective tissues such as skin, arteries, lungs and ligaments. They are laid down during development, and comprise a cross-linked elastin core within a template of fibrillin-based microfibrils. Their function is to endow tissues with the property of elastic recoil, and they also regulate the bioavailability of transforming growth factor β. Severe heritable elastic fibre diseases are caused by mutations in elastic fibre components; for example, mutations in elastin cause supravalvular aortic stenosis and autosomal dominant cutis laxa, mutations in fibrillin-1 cause Marfan syndrome and Weill–Marchesani syndrome, and mutations in fibulins-4 and -5 cause autosomal recessive cutis laxa. Acquired elastic fibre defects include dermal elastosis, whereas inflammatory damage to fibres contributes to pathologies such as pulmonary emphysema and vascular disease. This review outlines the latest understanding of the composition and assembly of elastic fibres, and describes elastic fibre diseases and current therapeutic approaches.

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“…Из-за потенциальной возможности дис-тального стеноза сосудов измерение артериального давления должно проводиться на всех четырех конеч-ностях [7]. Нейрососудистые аномалии при синдроме Вильямса могут приводить к инсульту, стеноз бры-жеечных артерий способствует развитию синдрома абдоминальной боли [8].…”

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