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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Do extracellular matrix protein expressions change with cyclic reproductive hormones in pelvic connective tissue from women with stress urinary incontinence
TL;DR: LTBP-1, LTBP-2, TGF-beta1, fibrillin-2 expressions are hormonally regulated in vaginal wall fibroblasts and differ in women affected by SUI when compared to controls, which suggest a mechanism to regulate TGF -beta1 activity in pelvic connective tissue.
Journal ArticleDOI
Thrombospondins: A Role in Cardiovascular Disease.
Dimitry A. Chistiakov,Alexandra A. Melnichenko,Veronika A. Myasoedova,Andrey V. Grechko,Alexander N. Orekhov +4 more
TL;DR: The development and evaluation of TSP-deficient animal models provided an option to assess the contribution of T SPs to cardiovascular pathology such as (myocardial infarction) MI, cardiac hypertrophy, heart failure, atherosclerosis, and aortic valve stenosis.
Journal Article
Contribution of the latent transforming growth factor-β binding protein 2 gene to etiology of primary open angle glaucoma and pseudoexfoliation syndrome.
Sahar Jelodari-Mamaghani,Ramona Haji-Seyed-Javadi,Fatemeh Suri,Naveed Nilforushan,Shahin Yazdani,Kambiz Kamyab,Elahe Elahi +6 more
TL;DR: Some LTBP2 sequence variations can contribute to the etiology of POAG and PEX glaucoma syndrome, and these genes and related ECM protein coding genes should be screened in larger cohorts with these diseases, which are common disorders and important to the public health.
Journal ArticleDOI
Transforming Growth Factor-β Signaling in Myogenic Cells Regulates Vascular Morphogenesis, Differentiation, and Matrix Synthesis
Mia Jaffe,Casilde Sesti,Ida M. Washington,Liang Du,Nagadhara Dronadula,Michael T. Chin,Donna B. Stolz,Elaine C. Davis,David A. Dichek +8 more
TL;DR: Effects of TGF-&bgr; on SMC gene expression appear to differ depending on the location of SMCs in the aorta, as well as matrix synthesis, and vascular morphogenesis.
Journal ArticleDOI
Systematic screening of lysyl oxidase-like (LOXL) family genes demonstrates that LOXL2 is a susceptibility gene to intracranial aneurysms.
Hiroyuki Akagawa,Akira Narita,Akira Narita,Haruhiko Yamada,Atsushi Tajima,Atsushi Tajima,Boris Krischek,Boris Krischek,Hidetoshi Kasuya,Tomokatsu Hori,Motoo Kubota,Naokatsu Saeki,Akira Hata,Tohru Mizutani,Ituro Inoue,Ituro Inoue +15 more
TL;DR: It is found that the SNPs of LOXL2 have an interactive effect with elastin (ELN) and LIM kinase 1 (LIMK1) that have been previously found to be associated with IA.
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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