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
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Patent
Lysyl oxidase-like 1 (LOXL1) and elastogenesis
Tiansen Li,Xiaoqing Liu +1 more
TL;DR: In this article, methods of treating and preventing conditions associated with a loss of elastic fibers are described, and methods of screening for agents useful in treating such conditions, and animal models are provided.
Journal ArticleDOI
Dynamics of elastin in liver fibrosis: Accumulates late during progression and degrades slowly in regression
Wei Chen,Xuzhen Yan,Anjian Xu,Yameng Sun,Bingqiong Wang,Tao Huang,Huan Wang,Min Cong,Ping Wang,Aiting Yang,Jidong Jia,Hong You +11 more
TL;DR: New general hallmarks of elastin levels and forms in progressive and regressive liver fibrosis are established and provided a foundation for further experimental investigation of the growing role ofElastin in Liver fibrosis regression.
Journal ArticleDOI
Pseudoexfoliation syndrome and pseudoexfoliation glaucoma
TL;DR: A modification du gene LOXL1, implique dans le metabolisme de certains composants elastiques de la matrice extracellulaire, lexposition naturelle aux rayons ultraviolets ou la consommation de cafe seraient impliquees as discussed by the authors.
Journal ArticleDOI
Lysyl oxidase-like 1 gene in the reversal of promoter risk allele in pseudoexfoliation syndrome.
Sushil Kumar Dubey,J. Fielding Hejtmancik,Subbaiah Ramasamy Krishnadas,Rajendrababu Sharmila,Aravind Haripriya,Periasamy Sundaresan +5 more
TL;DR: This is the first study to demonstrate the association of rs41435250 with PEX as well as reversal of the promoter risk allele, and the role of the LOXL1 gene in PEX pathogenesis will facilitate early detection in individuals at risk for this condition.
Journal ArticleDOI
DANCE/fibulin-5 promotes elastic fiber formation in a tropoelastin isoform-dependent manner.
Risa Nonaka,Satoshi Onoue,Hiroshi Wachi,Fumiaki Sato,Zsolt Urban,Barry Starcher,Yoshiyuki Seyama +6 more
TL;DR: New insights are provided into the initial steps of elastic fiber assembly and identify fibulin-5 and tropoelastin isoforms as potential targets for the regeneration of elastic fibers in vivo.
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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Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma.
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