Elastic fiber homeostasis requires lysyl oxidase-like 1 protein.
Xiao-Qing Liu,Yun Zhao,Jiangang Gao,Basil S. Pawlyk,Barry Starcher,Jeffrey A. Spencer,Hiromi Yanagisawa,J. Zuo,Tiansen Li +8 more
TLDR
It is shown that mice lacking the protein lysyl oxidase–like 1 (LOXL1) do not deposit normal elastic fibers in the uterine tract post partum and develop pelvic organ prolapse, enlarged airspaces of the lung, loose skin and vascular abnormalities with concomitant tropoelastin accumulation.Abstract:
Elastic fibers are components of the extracellular matrix and confer resilience1. Once laid down, they are thought to remain stable2, except in the uterine tract where cycles of active remodeling occur3. Loss of elastic fibers underlies connective tissue aging and important diseases including emphysema4,5,6,7. Failure to maintain elastic fibers is explained by a theory of antielastase-elastase imbalance8, but little is known about the role of renewal. Here we show that mice lacking the protein lysyl oxidase–like 1 (LOXL1) do not deposit normal elastic fibers in the uterine tract post partum and develop pelvic organ prolapse, enlarged airspaces of the lung, loose skin and vascular abnormalities with concomitant tropoelastin accumulation. Distinct from the prototypic lysyl oxidase (LOX), LOXL1 localizes specifically to sites of elastogenesis and interacts with fibulin-5. Thus elastin polymer deposition is a crucial aspect of elastic fiber maintenance and is dependent on LOXL1, which serves both as a cross-linking enzyme and an element of the scaffold to ensure spatially defined deposition of elastin.read more
Citations
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Age-related macular degeneration revisited--piecing the puzzle: the LXIX Edward Jackson memorial lecture.
TL;DR: Improved understanding of the underlying genetic susceptibility can identify targets to halt early disease and to prevent progression and vision loss and an integrated model of the pathogenesis of AMD is proposed.
Journal ArticleDOI
Coacervation of tropoelastin.
TL;DR: Tropoelastin coacervation is essential for progression to downstream elastogenic stages, and impairment of the process can result in elastin haploinsufficiency disorders such as supravalvular aortic stenosis.
Journal ArticleDOI
Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice
Precious J. McLaughlin,Qiuyun Chen,Masahito Horiguchi,Barry Starcher,J. Brett Stanton,Thomas J. Broekelmann,Alan D. Marmorstein,Brian S. McKay,Robert P. Mecham,Tomoyuki Nakamura,Lihua Y. Marmorstein,Lihua Y. Marmorstein +11 more
TL;DR: It is shown that lack of fibulin-4, an extracellular matrix molecule, abolishes elastogenesis and plays an irreplaceable role inElastogenesis, a major contributing factor in aging and diseases.
Journal ArticleDOI
Lysyl Oxidase-Like 2 as a New Poor Prognosis Marker of Squamous Cell Carcinomas
Héctor Peinado,Gema Moreno-Bueno,David Hardisson,Eduardo Pérez-Gómez,Vanesa Santos,Marta Mendiola,Juan I. de Diego,Manuel Nistal,Miguel Quintanilla,Francisco Portillo,Amparo Cano +10 more
TL;DR: The results show that LOXL2 can be used as a new poor prognosis indicator in human squamous cell carcinomas promoting malignant transformation by both SNAi1-dependent and SNAI1-independent pathways.
Journal ArticleDOI
Tissue mechanics, animal models, and pelvic organ prolapse: a review.
TL;DR: This review paper will discuss the different animal models that have been previously used to characterize the biomechanical properties of the vagina: including non-human primates, rodents, rabbits, and sheep.
References
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Journal ArticleDOI
Requirement for Macrophage Elastase for Cigarette Smoke-Induced Emphysema in Mice
TL;DR: Smoke-exposed MME-/- mice that received monthly intratracheal instillations of monocyte chemoattractant protein-1 showed accumulation of alveolar macrophages but did not develop air space enlargement, indicating that macrophage elastase is probably sufficient for the development of emphysema that results from chronic inhalation of cigarette smoke.
Journal ArticleDOI
Lysyl oxidase: Properties, specificity, and biological roles inside and outside of the cell
TL;DR: Although the three‐dimensional structure of LO has yet to be determined, the present treatise offers hypotheses based upon its primary sequence, which may underlie the prominent electrostatic component of its unusual substrate specificity as well as the catalysis‐suppressing function of the propeptide domain of prolysyl oxidase.
Journal ArticleDOI
Fibulin-5/DANCE is essential for elastogenesis in vivo
Tomoyuki Nakamura,Pilar Ruiz Lozano,Yasuhiro Ikeda,Yoshitaka Iwanaga,Aleksander Hinek,Susumu Minamisawa,Ching-Feng Cheng,Kazuhiro Kobuke,Nancy D. Dalton,Yoshikazu Takada,Kei Tashiro,John Ross,Tasuku Honjo,Kenneth R. Chien +13 more
TL;DR: It is reported that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization and may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibre in the skin, lung and vasculature.
Journal ArticleDOI
Effect of vaginal delivery on the pelvic floor: A 5‐year follow‐up
TL;DR: Evidence is provided for the hypothesis that pudendal neuropathy due to vaginal delivery persists and may worsen with time and for the effect of childbirth on the pelvic floor striated sphincter musculature.
Journal ArticleDOI
Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo
Hiromi Yanagisawa,Elaine C. Davis,Barry Starcher,Takashi Ouchi,Masashi Yanagisawa,James A. Richardson,Eric N. Olson +6 more
TL;DR: Fibulin-5-/- mice develop marked elastinopathy owing to the disorganization of elastic fibres, with resulting loose skin, vascular abnormalities and emphysematous lung, which resembles the cutis laxa syndrome in humans.
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