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
More filters
Journal ArticleDOI
Characterization of the molecular interaction between tropoelastin and DANCE/fibulin-5.
Hiroshi Wachi,Risa Nonaka,Fumiaki Sato,Kayoko Shibata-Sato,Marie Ishida,Saori Iketani,Iori Maeda,Koji Okamoto,Zsolt Urban,Satoshi Onoue,Yoshiyuki Seyama +10 more
TL;DR: The present study shows that fibulin-5 enhances elastic fiber formation in part by improving the self-association properties of tropoelastin.
Journal ArticleDOI
Lysyl Oxidase, A Critical Intra- and Extra-Cellular Target in the Lung for Cigarette Smoke Pathogenesis
TL;DR: Molecular mechanisms for CS damage to lung LO and its role in emphysema and cancer pathogenesis are discussed in this review.
Journal ArticleDOI
Quantification of Pelvic Organ Prolapse in Mice: Vaginal Protease Activity Precedes Increased MOPQ Scores in Fibulin 5 Knockout Mice
Cecilia K. Wieslander,David D. Rahn,Donald D. McIntire,Jesus F. Acevedo,Peter G. Drewes,Hiromi Yanagisawa,R. Ann Word +6 more
TL;DR: The results indicate that >90% of Fbln5−/− mice develop prolapse by 6 mo of age, even in the absence of vaginal delivery, and that increased vaginal protease activity precedes the development of prolapse.
Journal ArticleDOI
The role of neutrophil elastase in elastin metabolism of pelvic tissues from women with stress urinary incontinence.
TL;DR: This work studied neutrophil elastase and matrix metalloproteinase activities in vaginal tissues from premenopausal women with stress urinary incontinence (SUI) and found altered elastin metabolism is implicated in pelvic floor disorders.
Journal ArticleDOI
Recent updates on the molecular network of elastic fiber formation.
Seung Jae Shin,Hiromi Yanagisawa +1 more
TL;DR: FBLN5, FBLN4 and LTBP4 have been demonstrated to play crucial roles in elastogenesis through knockout studies in mice and using these molecules as a platform and expanding the elastic fiber network through the generation of an interactome map is provided.
References
More filters
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.
Related Papers (5)
Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma.
Gudmar Thorleifsson,Kristinn P. Magnusson,Patrick Sulem,G. Bragi Walters,Daniel F. Gudbjartsson,Hreinn Stefansson,Thorlakur Jonsson,Adalbjorg Jonasdottir,Aslaug Jonasdottir,Gerdur Stefansdottir,Gisli Masson,Gudmundur A. Hardarson,H. Petursson,Arsaell Arnarsson,Mehdi Motallebipour,Ola Wallerman,Claes Wadelius,Jeffrey R. Gulcher,Unnur Thorsteinsdottir,Augustine Kong,Fridbert Jonasson,Kari Stefansson +21 more