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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Engraftment of neonatal lung fibroblasts into the normal and elastase-injured lung.
Ping-Ping Kuang,Edgar C. Lucey,David C. Rishikof,Donald E. Humphries,Daniel Bronsnick,Ronald H. Goldstein +5 more
TL;DR: The endotracheal delivery of fibroblasts to the lung parenchyma is explored as a means of repairing damaged alveolar structures directly or indirectly for the delivery of transgenes.
Journal ArticleDOI
Induction of the myofibroblast phenotype following elastolytic injury to mouse lung
David C. Rishikof,Edgar C. Lucey,Edgar C. Lucey,Ping-Ping Kuang,Gordon L. Snider,Ronald H. Goldstein,Ronald H. Goldstein +6 more
TL;DR: The data suggest that repair mechanisms following elastolytic injury are confined to overtly damaged alveolar structures and involve the induction of the myofibroblast phenotype, and that α1(I) collagen and elastin mRNA expression were not induced in areas of normal lung adjacent to damaged lung.
Journal ArticleDOI
Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue
TL;DR: The impact of reactive oxygen species (ROS) and oxidative stress on the onset and/or progression of diseases that directly affect connective tissue and have a genetic origin are reviewed.
Journal ArticleDOI
Association between polymorphisms in lysyl oxidase-like 1 and susceptibility to pseudoexfoliation syndrome and pseudoexfoliation glaucoma.
TL;DR: The meta-analysis suggested that LOXL1 rs1048661 TT, rs3825942 AA, and rs2165241 CC were associated with a reduced risk of developing PEXS/PEXG.
Journal ArticleDOI
Alternatively spliced lysyl oxidase-like 4 isoforms have a pro-metastatic role in cancer
Shulamit Sebban,Regina Golan-Gerstl,Rotem Karni,Olga Vaksman,Ben Davidson,Ben Davidson,Reuven Reich +6 more
TL;DR: It is shown that both splice variants have a positive effect on the metastatic potential of cells in vitro and on tumor progression in vivo, and that LOXL4 is a possible splicing target of the oncogenic splicing factors SRSF1 and hnRNP A1.
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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