Annexin A2, autoimmunity, anxiety and depression

Weiss, Ronen; Bitton, Almog; Shimon, Marina Ben; Goldman, Shirin Elhaik; Nahary, Limor; Cooper, Isabella D.; Benhar, Itai; Pick, Chaim G.; Chapman, Joab

doi:10.1016/j.jaut.2016.06.011

Cited by 27 publications

(19 citation statements)

References 54 publications

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“…ANXA2 has broad impact in fundamental biological processes including cell proliferation, endocytosis, exocytosis, cytoskeletal rearrangement, intracellular signal transduction, fibrinolysis response, and cell migration 4–10 . Importantly, extracellular ANXA2 is associated with many human diseases, such as cancers, inflammatory disorders and autoimmune diseases 11–13 . It has been previously reported that ANXA2, which lacks any signal peptide for targeting to the endoplasmic reticulum (ER), is transported onto the cell surface 14 .…”

Section: Introductionmentioning

confidence: 99%

Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells

Chen

Fang

Cheng

et al. 2017

Sci Rep

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Annexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the extracellular secretion of ANXA2 in lung epithelial cells. We observed colocalization of ANXA2-containing autophagosomes with multivesicular bodies (MVBs) after IFN-γ stimulation, followed by exosomal release. IFN-γ-induced exophagic release of ANXA2 could not be observed in ATG5-silenced or mutant RAB11-expressing cells. Furthermore, knockdown of RAB8A and RAB27A, but not RAB27B, reduced IFN-γ-triggered ANXA2 secretion. Surface translocation of ANXA2 enhanced efferocytosis by epithelial cells, and inhibition of different exophagic steps, including autophagosome formation, fusion of autophagosomes with MVBs, and fusion of amphisomes with plasma membrane, reduced ANXA2-mediated efferocytosis. Our data reveal a novel route of IFN-γ-induced exophagy of ANXA2.

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Section: Introductionmentioning

confidence: 99%

Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells

Chen

Fang

Cheng

et al. 2017

Sci Rep

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“…The design and manufacture of this microarray provide a technical tool for the realization of this purpose. Because this microarray contains antigens from virus, such as S protein, also annexin a2, hnRNP A2/B1 are classical endothelial cell antigens of host [ 28 , 29 ]. This chip also has further value in studying the immune response after virus infection.…”

Section: Discussionmentioning

confidence: 99%

Establishment and validation of a drug-target microarray for SARS-CoV-2

Chen

Zeng

2020

Biochemical and Biophysical Research Communications

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COVID-19 has become one of the worst epidemic in the world, currently already more than four million people have been infected, which probably co-exist with human beings, and has a significant impact on the global economy and political order. In the process of fighting against the epidemic in China, the clinical value of a variety of herbal medicines has been recognized and written into the clinical application guide. However, their effective molecular mechanism and potential targets are still not clear. Pathology and pharmacology research will gradually attract attention in the post-epidemic outbreak term. Here, we constructed a COVID-19 protein microarray of potential therapy targets, which contains the main drug targets to the SARS-CoV-2 virus and the anti-virus, anti-inflammatory cellar targets of the host. Series of quality controls test has been carried out, which showed that it could be applied for drug target screening of bio-active natural products. The establishment of this microarray will provide a useful tool for the study of the molecular pharmacology of natural products.

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“…Recombinant human (98% identical to the mouse ANXA2) ANXA2+His-tag was expressed in E. coli cells and purified using a His-Trap column (GE Healthcare) as previously described. 24 , 25 …”

Section: Methodsmentioning

confidence: 99%

“…Recombinant human (98% identical to the mouse ANXA2) ANXA2þHis-tag was expressed in E. coli cells and purified using a His-Trap column (GE Healthcare) as previously described. 24,25 Human subjects Serum samples were collected from 4 patients with primary APS, mean age for patients was 44 AE 5, and from normal anonymous age matched controls as part of a larger study (EASI-ANA #8112-10). The definition of APS was according to the 2006 classification criteria and specifically all patients exhibited high levels of antibodies to cardiolipin/beta2glycoprotein1 or anticoagulant together with clinical vascular involvement.…”

Section: Expression and Purification Of The Recombinant Anxa2 Proteinmentioning

confidence: 99%

“…23 We have established an animal model by immunizing mice with recombinant highly purified ANXA2. 24,25 These animals do not develop antibodies to b2GPI and display behavioral changes unlike those found in b2GPI-immunized mice. In the present study, we assessed whether anti-ANXA2 antibodies can play a pathological role in thrombosis associated disease using the middle cerebral artery occlusion (MCAo) stroke model in the ANXA2 immunized mice model compared to adjuvant immunized controls.…”

Section: Introductionmentioning

confidence: 98%

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Autoantibodies to Annexin A2 and cerebral thrombosis: Insights from a mouse model

Weiss

Bushi

Mindel

et al. 2021

Lupus

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Introduction Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by thromboembolic events, recurrent spontaneous abortions and elevated titers of circulating antiphospholipid antibodies. In addition, the presence of antiphospholipid antibodies seems to confer a fivefold higher risk for stroke or transient ischemic attack. Although the major antigen of APS is β2 glycoprotein I, it is now well established that antiphospholipid antibodies are heterogeneous and bind to various targets. Recently, antibodies to Annexin A2 (ANXA2) have been reported in APS. This is of special interest since data indicated ANXA2 as a key player in fibrinolysis. Therefore, in the present study we assessed whether anti-ANXA2 antibodies play a pathological role in thrombosis associated disease. Materials and Methods Mice were induced to produce anti-ANXA2 antibodies by immunization with ANXA2 (iANXA2) and control mice were immunized with adjuvant only. A middle cerebral artery occlusion stroke model was applied to the mice. The outcome of stroke severity was assessed and compared between the two groups. Results Our results indicate that antibodies to ANXA2 lead to a more severe stroke as demonstrated by a significant larger stroke infarct volume (iANXA2 133.9 ± 3.3 mm3 and control 113.7 ± 7.4 mm3; p = 0.017) and a more severe neurological outcome (iANXA2 2.2 ± 0.2, and control 1.5 ± 0.18; p = 0.03). Conclusions This study supports the hypothesis that auto-antibodies to ANXA2 are an independent risk factor for cerebral thrombosis. Consequently, we propose screening for anti-ANXA2 antibodies should be more widely used and patients that exhibit the manifestations of APS should be closely monitored by physicians.

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Annexin A2, autoimmunity, anxiety and depression

Cited by 27 publications

References 54 publications

Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells

Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells

Establishment and validation of a drug-target microarray for SARS-CoV-2

Autoantibodies to Annexin A2 and cerebral thrombosis: Insights from a mouse model

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