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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Journal ArticleDOI
The Role of the Lysyl Oxidases in Tissue Repair and Remodeling: A Concise Review.
TL;DR: The role of the LOXs in inflammation phase, proliferation phase, and tissue remodeling phase of the repair process is focused on to shed light on the understanding of its potential in tissue repair and provide up to date therapeutic strategies towards related injuries.
Journal ArticleDOI
A model two-component system for studying the architecture of elastin assembly in vitro.
TL;DR: It is found that assembly of tropoelastin molecules in ELs are highly enriched for a defined subset of cross-links, leading to a model of the molecular architecture of elastin assembly in vitro.
Journal ArticleDOI
Regulation of cellular senescence by extracellular matrix during chronic fibrotic diseases
Kaj E C Blokland,Simon D. Pouwels,Michael Schuliga,Darryl A. Knight,Darryl A. Knight,Darryl A. Knight,Janette K. Burgess +6 more
TL;DR: This review explores and summarises the current knowledge around how aberrant ECM potentially influences the senescent phenotype in chronic fibrotic diseases, and explores the possibility for interventions in the ECM–senescence regulatory pathways for therapeutic potential in chronic fibre diseases.
Journal ArticleDOI
Lower urogenital tract anatomical and functional phenotype in lysyl oxidase like-1 knockout mice resembles female pelvic floor dysfunction in humans.
Una J. Lee,A. Marcus Gustilo-Ashby,Firouz Daneshgari,Mei Kuang,Drina Vurbic,Dan Li Lin,Dan Li Lin,Christopher A Flask,Tiansen Li,Margot S. Damaser +9 more
TL;DR: It is concluded that LOXL1 warrants further investigation in the pathphysiology of FPFD, and the increase in elastin clusters in the urethra of LoXL1-KO mice with POP suggests thatElastin disorganization may lead to functional abnormalities.
Journal ArticleDOI
Collagen and elastin cross-linking is altered during aberrant late lung development associated with hyperoxia
Ivana Mižíková,Jordi Ruiz-Camp,Heiko Steenbock,Alicia Madurga,István Vadász,Susanne Herold,Konstantin Mayer,Werner Seeger,Jürgen Brinckmann,Rory E. Morty,Rory E. Morty +10 more
TL;DR: It is demonstrated that collagen and elastin cross-linking are perturbed during the arrested alveolarization of developing mouse lungs exposed to hyperoxia.
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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