Annexin expression in inflammatory myopathies

Probst‐Cousin, Stefan; Berghoff, Corinna; Neundörfer, B.; Heuss, Dieter

doi:10.1002/mus.20077

Cited by 22 publications

(17 citation statements)

References 54 publications

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“…Thus, these results present the possibility that rVvpE influences the structure and localization of ANXA2 through lipid rafts to promote proinflammatory signaling in intestinal epithelial cells. Compelling evidence further supported the critical role of ANXA2 in inflammatory myopathies (43) as well as in inflammatory bowel disease (44). Taken together, our finding that VvpE induces proinflammatory responses via an ANXA2-dependent mechanism provides information about the important mechanisms of pathogen-induced cell death during V. vulnificus infection.…”

Section: Discussionsupporting

confidence: 48%

Vibrio vulnificus VvpE Stimulates IL-1β Production by the Hypomethylation of the IL-1β Promoter and NF-κB Activation via Lipid Raft–Dependent ANXA2 Recruitment and Reactive Oxygen Species Signaling in Intestinal Epithelial Cells

Lee

Jung

Song

et al. 2015

The Journal of Immunology

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An inflammatory response is a hallmark of necrosis evoked by bacterial pathogens. Vibrio vulnificus, VvpE, is an elastase that is responsible for tissue necrosis and inflammation; however, the molecular mechanism by which it regulates host cell death has not been characterized. In the present study, we investigate the cellular mechanism of VvpE with regard to host cell death and the inflammatory response of human intestinal epithelial (INT-407) cells. The recombinant protein (r)VvpE (50 pg/ml) caused cytotoxicity mainly via necrosis coupled with IL-1β production. The necrotic cell death induced by rVvpE is highly susceptible to the knockdown of annexin A (ANXA)2 and the sequestration of membrane cholesterol. We found that rVvpE induces the recruitment of NADPH oxidase 2 and neutrophil cytosolic factor 1 into membrane lipid rafts coupled with ANXA2 to facilitate the production of reactive oxygen species (ROS). The bacterial signaling of rVvpE through ROS production is uniquely mediated by the phosphorylation of redox-sensitive transcription factor NF-κB. The silencing of NF-κB inhibited IL-1β production during necrosis. rVvpE induced hypomethylation and region-specific transcriptional occupancy by NF-κB in the IL-1β promoter and has the ability to induce pyroptosis via NOD-, LRR-, and pyrin domain–containing 3 inflammasome. In a mouse model of V. vulnificus infection, the mutation of the vvpE gene from V. vulnificus negated the proinflammatory responses and maintained the physiological levels of the proliferation and migration of enterocytes. These results demonstrate that VvpE induces the hypomethylation of the IL-1β promoter and the transcriptional regulation of NF-κB through lipid raft–dependent ANXA2 recruitment and ROS signaling to promote IL-1β production in intestinal epithelial cells.

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Section: Discussionsupporting

confidence: 48%

Vibrio vulnificus VvpE Stimulates IL-1β Production by the Hypomethylation of the IL-1β Promoter and NF-κB Activation via Lipid Raft–Dependent ANXA2 Recruitment and Reactive Oxygen Species Signaling in Intestinal Epithelial Cells

Lee

Jung

Song

et al. 2015

The Journal of Immunology

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“…Several members of the annexin family (e.g. annexins A1, A2, and A5) are differentially expressed in normal muscle relative to Duchenne muscular dystrophy, and the three annexins are highly expressed in macrophages and T cells in dystrophin-deficient muscle (18,43). The annexins could therefore have a role in the inflammatory response in muscular dystrophy, and MDC1A is indeed characterized by early-onset transient inflammation (44).…”

Section: Inflammation and Composition Of Fibrotic Tissue In Laminin ␣2mentioning

confidence: 99%

Quantitative Proteomic Analysis Reveals Metabolic Alterations, Calcium Dysregulation, and Increased Expression of Extracellular Matrix Proteins in Laminin α2 Chain–deficient Muscle

Oliveira

Matsumura

Fontes-Oliveira

et al. 2014

Molecular & Cellular Proteomics

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Congenital muscular dystrophy with laminin ␣2 chain deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by severe muscle weakness and delayed motor milestones. The genetic basis of MDC1A is well known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin ␣2 chain-deficient dy 3K /dy 3K mice, using multidimensional protein identification technology combined with tandem mass tags. Out of the approximately 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared with normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium, or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin ␣2 chain-deficient muscle might help in the design of future anti-fibrotic treatments. All MS data have been deposited in the ProteomeXchange with identi-

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“…First, tissues expressing annexin A1 include those mentioned above as known locales of plasma membrane disruption. Second, humans with Duchenne muscular dystrophy, in which the frequency of sacrolemma disruption is greatly increased, exhibit enhanced levels of skeletal muscle annexin (several family members) expression (13), and humans with dysferlin-related muscular dystrophy specifically exhibit an increase in annexin A1 expression (14). Third, Ca 2ϩ -activated annexin A1 can aggregate and, in some cases, fuse phospholipids bilayers (12).…”

mentioning

confidence: 99%

Requirement for Annexin A1 in Plasma Membrane Repair

McNeil

Rescher

Gerke

et al. 2006

Journal of Biological Chemistry

210

174

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Ca2؉ entering a cell through a torn or disrupted plasma membrane rapidly triggers a combination of homotypic and exocytotic membrane fusion events. These events serve to erect a reparative membrane patch and then anneal it to the defect site. Annexin A1 is a cytosolic protein that, when activated by micromolar Ca 2؉ , binds to membrane phospholipids, promoting membrane aggregation and fusion. We demonstrate here that an annexin A1 function-blocking antibody, a small peptide competitor, and a dominant-negative annexin A1 mutant protein incapable of Ca 2؉ binding all inhibit resealing. Moreover, we show that, coincident with a resealing event, annexin A1 becomes concentrated at disruption sites. We propose that Ca 2؉ entering through a disruption locally induces annexin A1 binding to membranes, initiating emergency fusion events whenever and wherever required.Plasma membrane disruption, a common form of cell injury, is provoked in many mammalian tissues by physiological levels of mechanical stress (1). Disease can result from a failure either to prevent or repair disruptions. In Duchenne muscular dystrophy, for example, normal muscle contractions result in a pathological level of disruption injury because of increased fiber fragility (2). In limb-girdle muscular dystrophy, on the other hand, the failure is in the repair of normally occurring disruptions (3). Indeed, membrane repair, or resealing, is the universal survival response that eukaryotic cells mount when confronted with a life-threatening disruption in the integrity of their plasma membrane.The mechanism of resealing is now well characterized at the cellular level. A large plasma membrane disruption (Ͼ1 m diameter) locally and rapidly (subsecond to second time scale) elicits Ca 2ϩ -activated, homotypic vesicle fusion (4, 5). The "patch" vesicle thus formed then fuses exocytotically with the plasma membrane surrounding the defect site, restoring barrier continuity (6, 7). Identification of the protein components of this process is under way, and members of the SNARE 2 family (membrane proteins thought to be required for many fusion events) are implicated in resealing (8). However, as an emergency response it must be rapid and Ca 2ϩ -responsive and yet capable of being activated with a great level of temporal and spatial flexibility. Therefore, it has been hypothesized that resealing-based fusion may utilize, in addition to canonical elements such as the SNAREs, a specialized subset of fusion components (9). Dysferlin, a Ca 2ϩ -activated membrane-binding protein that mediates exocytotic fusion events in nematodes (10), is one candidate emergency fusion component. Thus, it was recently shown that skeletal muscle cells from dysferlin null mice fail to reseal disruptions (3).One protein shown by immunolocalization and immunoprecipitation to associate with dysferlin in normal, undisturbed skeletal muscle is annexin A1 (11), a member of the annexin family of Ca 2ϩ -regulated membrane-binding proteins (12). This observation, as well as the following additional po...

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Annexin expression in inflammatory myopathies

Cited by 22 publications

References 54 publications

Vibrio vulnificus VvpE Stimulates IL-1β Production by the Hypomethylation of the IL-1β Promoter and NF-κB Activation via Lipid Raft–Dependent ANXA2 Recruitment and Reactive Oxygen Species Signaling in Intestinal Epithelial Cells

Vibrio vulnificus VvpE Stimulates IL-1β Production by the Hypomethylation of the IL-1β Promoter and NF-κB Activation via Lipid Raft–Dependent ANXA2 Recruitment and Reactive Oxygen Species Signaling in Intestinal Epithelial Cells

Quantitative Proteomic Analysis Reveals Metabolic Alterations, Calcium Dysregulation, and Increased Expression of Extracellular Matrix Proteins in Laminin α2 Chain–deficient Muscle

Requirement for Annexin A1 in Plasma Membrane Repair

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