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
Posttranscriptional Regulation of LOXL1 Expression Via Alternative Splicing and Nonsense-Mediated mRNA Decay as an Adaptive Stress Response.
Daniel Berner,Matthias Zenkel,Francesca Pasutto,Ursula Hoja,Panah Liravi,Gabriele C. Gusek-Schneider,Friedrich E. Kruse,Johannes Schödel,André Reis,Ursula Schlötzer-Schrehardt +9 more
TL;DR: Evidence is provided for a functional role of alternative splicing coupled to NMD in the posttranscriptional regulation of lysyl oxidase-like 1 (LOXL1) expression in response to pseudoexfoliation (PEX)-associated pathophysiologic factors and suggest this mechanism to represent a dynamic mode of adapting LOXL1 expression to PEX-associated environmental and nutritional cues.
Journal ArticleDOI
Splicing mutation in the fibrillin-1 gene associated with neonatal Marfan syndrome and severe pulmonary emphysema with tracheobronchomalacia.
TL;DR: The clinical course of an infant with neonatal Marfan syndrome that had the novel IVS31‐2A > G splice site mutation in fibrillin‐1 probably leads to abnormal splicing events.
Journal ArticleDOI
Lysyl Oxidase Enhances the Deposition of Tropoelastin through the Catalysis of Tropoelastin Molecules on the Cell Surface.
TL;DR: The data show that LOX deficiency or the inhibition of LOX enzyme activity leads to the loss of elastin deposition in skin fibroblast and suggests the possibility that lysine oxidation by LOX precedes tropoelastsin deposition onto microfibrils.
Journal ArticleDOI
Interactions between lysyl oxidases and ADAMTS proteins suggest a novel crosstalk between two extracellular matrix families.
Rohtem Aviram,Shelly Zaffryar-Eilot,Dirk Hubmacher,Hagar Grunwald,Joni M. Mäki,Johanna Myllyharju,Suneel S. Apte,Peleg Hasson +7 more
TL;DR: ADAMTSL2 stability and inter-molecular complexes may depend on the activity of lysyl oxidases, and it is demonstrated here that several members of the LOX and ADAMTS families interact with one another.
Journal ArticleDOI
Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall.
Kathleen Chin,Cecilia K. Wieslander,Haolin Shi,Sunil Balgobin,T. Ignacio Montoya,Hiromi Yanagisawa,R. Ann Word +6 more
TL;DR: It is indicated that vaginal fibulin-5 during development is crucial for baseline pelvic organ support and is also important for protection and recovery from parturition- and elastase-induced prolapse.
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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