The role of fibrillin and microfibril binding proteins in elastin and elastic fibre assembly

Godwin, Alan R.; Singh, Mukti; Lockhart-Cairns, Michael P.; Alanazi, Yasmene F.; Cain, Stuart A.; Baldock, Clair

doi:10.1016/j.matbio.2019.06.006

Cited by 99 publications

(72 citation statements)

References 149 publications

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“…members of the TGFβ superfamily). 64 Notably, GO analysis showed microfibril, TGFβ sequestration, and elastin terms overlapped only at the P3 timepoint ( Figure 5). The perinatal increase in abundance of these collagens and elastinmicrofibril axis proteins may provide mechanical integrity by transiently stabilizing the 3D fibrous medullary ray sheath and vertical fibers ( Figures 5, 7, 8).…”

Section: Discussionmentioning

confidence: 98%

3D mapping reveals a complex and transient interstitial matrix during murine renal development

Lipp

Jacobson

Schwarderer

et al. 2020

Preprint

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Background: The extracellular matrix (ECM) is a network of proteins and glycosaminoglycans that provides structural and biochemical cues to cells. In the kidney, the ECM is critical for nephrogenesis; however, the dynamics of ECM composition and how it relates to 3D structure during development is unknown. Methods: Using embryonic day (E)14.5, E18.5, postnatal day (P)3, and adult kidneys, we fractionated proteins based on differential solubilities, performed liquid chromatography tandem-mass spectrometry, and identified changes in ECM protein content (matrisome). Decellularized kidneys were stained for ECM proteins and imaged in 3D using confocal microscopy. Results: We observed an increase in interstitial ECM that connect the stromal mesenchyme to the basement membrane (TNXB, COL6A1, COL6A2, COL6A3) between the embryo and adult, and a transient elevation of interstitial matrix proteins (COL5A2, COL12A1, COL26A1, ELN, EMID1, FBN1, LTBP4, THSD4) at perinatal timepoints. Basement membrane proteins critical for metanephric induction (FRAS1, FREM2) were highest in the embryo, whereas proteins necessary for glomerular basement membrane integrity (COL4A3, COL4A4, COL4A5, LAMB2) were more abundant in the adult. 3D visualization revealed a complex interstitial matrix that dramatically changed over development, including the perinatal formation of fibrillar structures that appear to support the medullary rays. Conclusion: By correlating 3D ECM spatiotemporal organization with global protein abundance, we identified novel changes in the interstitial matrix during kidney development. This new information regarding the ECM in developing kidneys offers the potential to inform the design of regenerative scaffolds that can guide nephrogenesis in vitro.

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Section: Discussionmentioning

confidence: 98%

3D mapping reveals a complex and transient interstitial matrix during murine renal development

Lipp

Jacobson

Schwarderer

et al. 2020

Preprint

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“…10 A notable microfibrillar protein is fibrillin, which interacts with other proteins to aid assembly, function, and long-term stability of the elastic fibres. 10 Smooth muscle cells induce vasodilation and constriction. Heterogenous origins of smooth muscle cells have recently been reported in the thoracic aorta and provide a better insight into the variable susceptibilities to disease in different parts of the aorta.…”

Section: Biology Of the Thoracic Aortamentioning

confidence: 99%

Bio-chemo-mechanics of the thoracic aorta

2021

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The pathophysiology of thoracic aortic aneurysms and dissections are poorly understood, despite high mortality associated with the diseases. An evidence review was conducted to examine the biomechanical, chemical and genetic factors involved in thoracic aortic pathology. The composition of connective tissue and smooth muscle cell action can mediate important mechanical properties that allow the thoracic aorta to withstand and transmit pressures. Genetic syndromes can affect connective tissue and signalling proteins that interrupt smooth muscle function, leading to tissue failure. There are complex interplaying factors that maintain thoracic aortic function in health and disrupt in disease, signifying an area for extensive research.

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“…This phenotype resembles that of Fbn1 C1039G/+ , a mouse model of Marfan syndrome (MFS) characterized by a low incidence of aortic dissections and ruptures compared to other MFS mouse models [126]. In these 'Marfan mice', the introduced Fbn1 mutation C1039G disrupts the microfibril scaffold, which has complex knock-on effects (including decreased ADAMTS-1 protein levels) owing to the many mechanistic complexities of the fibrillin microfibril niche and its roles in elastic fibre formation, growth factor signalling and VSMC biology [127,128]. However, in human aortic aneurisms, ADAMTS-1 levels are either unchanged or increased [30,129,130].…”

Section: Adamts-1: Friend (In Taad) or Foe (In Atherosclerosis)?mentioning

confidence: 99%

ADAMTS proteases in cardiovascular physiology and disease

Santamaria

Groot

2020

Open Biol.

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The a disintegrin-like and metalloproteinase with thrombospondin motif (ADAMTS) family comprises 19 proteases that regulate the structure and function of extracellular proteins in the extracellular matrix and blood. The best characterized cardiovascular role is that of ADAMTS-13 in blood. Moderately low ADAMTS-13 levels increase the risk of ischeamic stroke and very low levels (less than 10%) can cause thrombotic thrombocytopenic purpura (TTP). Recombinant ADAMTS-13 is currently in clinical trials for treatment of TTP. Recently, new cardiovascular roles for ADAMTS proteases have been discovered. Several ADAMTS family members are important in the development of blood vessels and the heart, especially the valves. A number of studies have also investigated the potential role of ADAMTS-1, -4 and -5 in cardiovascular disease. They cleave proteoglycans such as versican, which represent major structural components of the arteries. ADAMTS-7 and -8 are attracting considerable interest owing to their implication in atherosclerosis and pulmonary arterial hypertension, respectively. Mutations in the ADAMTS19 gene cause progressive heart valve disease and missense variants in ADAMTS6 are associated with cardiac conduction. In this review, we discuss in detail the evidence for these and other cardiovascular roles of ADAMTS family members, their proteolytic substrates and the potential molecular mechanisms involved.

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The role of fibrillin and microfibril binding proteins in elastin and elastic fibre assembly

Cited by 99 publications

References 149 publications

3D mapping reveals a complex and transient interstitial matrix during murine renal development

3D mapping reveals a complex and transient interstitial matrix during murine renal development

Bio-chemo-mechanics of the thoracic aorta

ADAMTS proteases in cardiovascular physiology and disease

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