title: The complexity of elastic fibre biogenesis in the skin--a perspective to the clinical heterogeneity of cutis laxa.
abstract: Elastic fibres are critical connective tissue components providing elasticity and resilience to skin and other tissues. These fibres are composed of elastin and a number of elastin-associated microfibrillar proteins that assemble in a complex fibre network in a multi-step process. Multiple cellular processes, including mitochondrial function, specific molecules in the secretory pathways and temporally and spatially ordered production of elastic fibre components, are required for the biogenesis of functional elastic fibres. Abnormalities in these processes can lead to loss of functional elastic fibres manifesting phenotypically as a skin disease. The paradigm of elastic fibre diseases affecting the skin is cutis laxa, a clinically and genetically heterogeneous group of disorders characterized by loose and sagging skin, frequently associated with extracutaneous manifestations in the lungs and the arterial blood vessels. The complexity of cutis laxa is emphasized by the fact that as many as 10 distinct genes can harbour mutations in this and related disorders. Understanding of the pathomechanistic pathways involved in perturbed elastic fibre assembly in cutis laxa provides information potentially helpful for the development of molecular strategies towards treatment of these, currently intractable, diseases.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. Jouni.Uitto@Jefferson.edu
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Urban
mesh_terms: D001158:Arteries / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics; D003483:Cutis Laxa / Q000175:diagnosis / Q000473:pathology*; D004547:Elastic Tissue / Q000473:pathology*; D004549:Elastin / Q000235:genetics; D005808:Genes, Recessive; D006801:Humans; D008171:Lung Diseases / Q000150:complications / Q000473:pathology; D020894:Microfibrils / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D012867:Skin / Q000473:pathology*
chemical_list: D004549:Elastin