Matrix modeling and remodeling: A biological interplay regulating tissue homeostasis and diseases

Karamanos, Nikos K.; Theocharis, Achilleas D.; Neill, Thomas; Iozzo, Renato V.

doi:10.1016/j.matbio.2018.08.007

Cited by 201 publications

(147 citation statements)

References 140 publications

(130 reference statements)

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“…The present study revealed that, compared with normal prostate, both low-grade and high-grade PCa have decreased expression of many ECM and plasma membrane proteins, which form large putative PPI networks. The ECM remodeling is probably due to increased proteolysis by matrix metalloproteinases and extracellular vesicles [59]. The most striking difference between low-grade and high-grade PCa is that only small PPI networks were more abundant in the former group, whereas a large PPI network was upregulated in the latter group.…”

Section: The Putative Ppi Network Of Depsmentioning

confidence: 99%

Quantitative Proteomic Analysis of Prostate Tissue Specimens Identifies Deregulated Protein Complexes in Primary Prostate Cancer

Zhou

Yan

Wang

et al. 2018

Preprint

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Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and a leading cause of mortality among males in developed countries. However, our understanding of the global changes of protein complexes within PCa tissue specimens remains very limited, although it has been well recognized that protein complexes carry out essentially all major processes in living organisms and that their deregulation drives the pathogenesis and progression of various diseases. By coupling tandem mass taggingsynchronous precursor selection-mass spectrometry/mass spectrometry/mass spectrometry (TMT-SPS-MS3) with differential expression and co-regulation analyses, the present study compared the differences between protein complexes in normal prostate, low-grade PCa, and high-grade PCa tissue specimens.Globally, a large downregulated putative protein-protein interaction (PPI) network was detected in both low-grade and high-grade PCa, yet a large upregulated putative PPI network was only detected in highgrade but not low-grade PCa, compared with normal controls. To identify specific protein complexes that are deregulated in PCa, quantified proteins were mapped to protein complexes in CORUM, a collection of experimentally verified mammalian protein complexes. Differential expression analysis suggested that mitochondrial ribosomes and the fibrillin-associated protein complex were significantly overexpressed, whereas the ITGA6-ITGB4-Laminin10/12 and the P2X7 receptor signaling complexes were significantly downregulated, in PCa compared with normal prostate. Moreover, differential co-regulation analysis indicated that the assembly levels of some nuclear protein complexes involved in RNA synthesis and processing were significantly increased in low-grade PCa, and those of mitochondrial complex I and its subcomplexes were significantly increased in high-grade PCa, compared with normal prostate. In summary, the study represents the first global and quantitative comparison of protein complexes in prostate tissue specimens. It is expected to enhance our understanding of the molecular mechanisms underlying PCa development and progression in human patients, as well as lead to the discovery of novel biomarkers and therapeutic targets for precision management of PCa.

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Section: The Putative Ppi Network Of Depsmentioning

confidence: 99%

Quantitative Proteomic Analysis of Prostate Tissue Specimens Identifies Deregulated Protein Complexes in Primary Prostate Cancer

Zhou

Yan

Wang

et al. 2018

Preprint

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“…A hallmark of decorin bioactivity is the dual property of being anti-angiogenic (13,15,27,32,86,87) and pro-autophagic (18,20,28, [46][47][48]. Moreover, the Dcn gene itself is an autophagic-inducible gene (88).…”

Section: Decorin Evokes Intracellular Degradation Of Vegfa Via Autophmentioning

confidence: 99%

Catabolic degradation of endothelial VEGFA via autophagy

Neill

Chen

Buraschi

et al. 2020

Journal of Biological Chemistry

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Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion of autophagy-related 5 (ATG5), results in accumulation of intracellular VEGFA, indicating that VEGFA is a basal autophagic substrate. Mechanistically, decorin increased the VEGFA clearance rate by augmenting autophagic flux, a process that required RAB24 member RAS oncogene family (RAB24), a small GTPase that facilitates the disposal of autophagic compartments. We validated these findings by demonstrating the physiological relevance of this process in vivo. Mice starved for 48 h exhibited a sharp decrease in overall cardiac and aortic VEGFA that could be blocked by systemic chloroquine treatment. Thus, our findings reveal a unified mechanism for the metabolic control of endothelial VEGFA for autophagic clearance in response to decorin and canonical pro-autophagic stimuli. We posit that the VEGFR2/AMPK/PEG3 axis integrates the anti-angiogenic and pro-autophagic bioactivities of decorin as the molecular basis for tumorigenic suppression. These results support future therapeutic use of decorin as a next-generation protein therapy to combat cancer.

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“…In some cases, proenzymes are associated with TIMP (low concentration) for correct activation; for example, the MMP-14/TIMP-2/proMMP-2 ternary complex. MMPs may be associated with other ECM components, such as proteoglycans and GAGs, leading to their specific localization in the cellular perimeter or at ECM sites distant from the cell secretion point (Van den Steen et al, 2001;Hernandez-Barrantes et al, 2002;Ra and Parks, 2007;Gabison et al, 2009;Hadler-Olsen et al, 2011;Piperi and Papavassiliou, 2012;Rietz and Spiers, 2012;Li et al, 2014;Arpino et al, 2015;Karamanos et al, 2019).…”

Section: Mmp Familymentioning

confidence: 99%

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

Paiva

Maas

Santos

et al. 2019

Front. Cell Dev. Biol.

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Craniofacial development comprises a complex process in humans in which failures or disturbances frequently lead to congenital anomalies. Cleft lip with/without palate (CL/P) is a common congenital anomaly that occurs due to variations in craniofacial development genes, and may occur as part of a syndrome, or more commonly in isolated forms (non-syndromic). The etiology of CL/P is multifactorial with genes, environmental factors, and their potential interactions contributing to the condition. Rehabilitation of CL/P patients requires a multidisciplinary team to perform the multiple surgical, dental, and psychological interventions required throughout the patient's life. Despite progress, lip/palatal reconstruction is still a major treatment challenge. Genetic mutations and polymorphisms in several genes, including extracellular matrix (ECM) genes, soluble factors, and enzymes responsible for ECM remodeling (e.g., metalloproteinases), have been suggested to play a role in the etiology of CL/P; hence, these may be considered likely targets for the development of new preventive and/or therapeutic strategies. In this context, investigations are being conducted on new therapeutic approaches based on tissue bioengineering, associating stem cells with biomaterials, signaling molecules, and innovative technologies. In this review, we discuss the role of genes involved in ECM composition and remodeling during secondary palate formation and pathogenesis and genetic etiology of CL/P. We also discuss potential therapeutic approaches using bioactive molecules and principles of tissue bioengineering for state-of-the-art CL/P repair and palatal reconstruction.

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Matrix modeling and remodeling: A biological interplay regulating tissue homeostasis and diseases

Cited by 201 publications

References 140 publications

Quantitative Proteomic Analysis of Prostate Tissue Specimens Identifies Deregulated Protein Complexes in Primary Prostate Cancer

Quantitative Proteomic Analysis of Prostate Tissue Specimens Identifies Deregulated Protein Complexes in Primary Prostate Cancer

Catabolic degradation of endothelial VEGFA via autophagy

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

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