Histone modification of pain-related gene expression in spinal cord neurons under a persistent postsurgical pain-like state by electrocautery.

Chronic postsurgical pain (CPSP) is a serious problem. We developed a mouse model of CPSP induced by electrocautery and examined the mechanism of CPSP. In this mouse model, while both incision and electrocautery each produced acute allodynia, persistent allodynia was only observed after electrocautery. Under these conditions, we found that the mRNA levels of Small proline rich protein 1A (Sprr1a) and Annexin A10 (Anxa10), which are the key modulators of neuropathic pain, in the spinal cord were more potently and persistently increased by electrocautery than by incision. Furthermore, these genes were overexpressed almost exclusively in chronic postsurgical pain-activated neurons. This event was associated with decreased levels of tri-methylated histone H3 at Lys27 and increased levels of acetylated histone H3 at Lys27 at their promoter regions. On the other hand, persistent allodynia and overexpression of Sprr1a and Anxa10 after electrocautery were dramatically suppressed by systemic administration of GSK-J4, which is a selective H3K27 demethylase inhibitor. These results suggest that the effects of electrocautery contribute to CPSP along with synaptic plasticity and epigenetic modification.

Annexin A10 Expression Is Associated With Poor Prognosis in Small Bowel Adenocarcinoma.

BACKGROUND/AIM: Small bowel adenocarcinoma (SBA) is a relatively rare malignant epithelial neoplasm. Thus, little is known about prognostic biomarkers of SBA. Annexin A10 (ANXA10) is a member of the annexin family. The significance of ANXA10 expression in SBA is unclear. This is the first study to examine the expression of ANXA10 in SBA. MATERIALS AND METHODS: We immunohistochemically evaluated ANXA10 expression of SBA and studied the relationship between ANXA10 expression and clinicopathological factors. RESULTS: ANXA10 expression was detected in 17 (56.7%) of 30 SBA cases and was significantly associated with poor overall survival. Univariate predictors for poor prognosis were tumour size (p=0.017) and ANXA10 expression (p=0.026). In multivariate analysis, ANXA10 expression (p=0.038) and tumour size (p=0.024) were found to be independent predictors of poor prognosis. CONCLUSION: ANXA10 could be a new prognostic biomarker for SBA.

Expression of the Serrated Markers Annexin A10 or Gremlin1 in Colonic Adenocarcinomas: Morphology and Prognostic Values.

Describe clinical, histological and molecular charatcteristics and prognosis values of the serrated candidate markers AnnexinA10 and Gremlin1 in colon adenocarcinomas. Immunohistochemical expression of AnnexinA10 and Gremlin1 was evaluated on 346 colonic adenocarcinomas. Clinicopathological, molecular features and prognostic characteristics were then evaluated. A total of 40 colonic adenocarcinomas expressed AnnexinA10 (11.6%) and, 115 expressed Gremlin1 (40.4%). AnnexinA10 expression was significantly associated, on univariate analyses, with female gender (p = 0.03), right tumor location (p < 0.001), differentiation grade 3 (p < 0.001), serrated adenocarcinoma subtype (p < 0.001), serrated (p < 0.001), medullary (p = 0.005), and mucinous component (p = 0.004), cytoplasmic eosinophilia (p < 0.001), discernible nuclei (p = 0.001), preserved polarity (p < 0.001), lymphatic invasion (p = 0.01), BRAFV600E mutation (p < 0.001), MSI-H status (p < 0.001) and CIMP-H status (p = 0.019). Multivariate analyses revealed that mucinous component (p = 0.002), lymphatic invasion (p = 0.02) and BRAFV600E mutation (p < 0.001) were independently associated with AnnexinA10 expression. In addition, AnnexinA10 was an indicator of poorer overall survival (OS) in UICC stage IV adenocarcinomas (p = 0.01) only. Gremlin1 expression was neither associated with serrated adenocarcinoma subtype (p = 0.51) nor with AnnexinA10 expression (p = 0,31), but was significantly associated, in univariate analysis with male gender (p = 0.002), younger age (p = 0.002), left tumor location (p = 0.04), and MSS status (p = 0.03). Gremlin1 expression was associated with better OS only in UICC stage III colon adenocarcinomas (p = 0.006). Colon adenocarcinomas expressing AnnexinA10 have distinct clinico-pathological and molecular features. AnnexinA10 expression is an indicator of poorer OS in UICC stage IV patients. Gremlin1 expression is not associated with serrated adenocarcinomas subtype. Its expression was associated with better OS in UICC Stage III patients.

Prognostic Significance of Increased Expression of Annexin A10 (ANXA10) in Serous Epithelial Ovarian Cancer.

BACKGROUND Epithelial ovarian cancer (EOC) is a gynecological malignancy that is associated with high mortality. Annexin A10 (ANXA10) is variably expressed in several types of human malignancy, but its role and clinical significance in EOC remain unknown. This study aimed to investigate the role of ANXA10 in EOC cells in vitro and to study the association between the protein expression levels of the ANXA10 in tumor tissue from patients with serous EOC and clinical outcome. MATERIAL AND METHODS The expression of ANXA10 was studied in 118 cases of serous EOC and in the ovarian cancer cell lines, SKOV-3, HO9810, HO8910PM, and OVCAR3 with immunohistochemistry and Western blot. Correlation between ANXA10 expression and clinicopathological variables and patient outcome were evaluated, including with Kaplan-Meier survival curves, univariate analysis with the log-rank test, and the multivariate analysis with the Cox-regression model. RESULTS ANXA10 was expressed by cells in the ovarian cancer cell lines. Patients with low expression and high expression of ANXA10 were 61.86% (73/118) and 38.14% (45/118), respectively. High expression of ANXA10 was correlated with poor response to chemotherapy (P=0.034), the presence of lymphatic invasion (P=0.043), and the International Federation of Gynecology and Obstetrics (FIGO) advanced stage (P=0.033), which were all associated with lower survival rates of serous EOC. Increased expression of ANXA10 was identified as an independent prognostic biomarker of serous EOC (HR=1.73; 95% CI, 1.01-2.98; P=0.046). CONCLUSIONS Increased expression of ANXA10 was an independent prognostic marker in patients with serous EOC.

Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels.

Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (for ICC) or to palliation (for mPDAC). Beyond the validation of recently published potential biomarkers for PDAC (primary or metastatic) in a large cohort, we assessed diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) from ICC. In a training set of 87 ICC and 88 pPDAC, our previously identified biomarkers Annexin A1 (ANXA1), ANXA10, and ANXA13 were tested and compared with 11 published biomarkers or panels (MUCIN 1, Agrin, S100P, MUC5 AC, Laminin, VHL, CK 17, N-Cadherin, ELAC2, PODXL and HSPG2). Biomarkers with best results were further tested in an independent series of biopsies of 27 ICC and 36 mPDAC. Highest AUC values (between 0.72 and 0.84) for the discrimination between ICC and pPDAC were found in the training set for Annexin A1, Annexin A10, MUC5 AC, CK17, and N-Cadherin. These markers were further tested on an independent series of liver biopsies containing ICC or mPDAC. Diagnostic characteristics were evaluated for individual markers as well as for 3× panels. ANXA 10 showed the highest diagnostic potential of all single markers, correctly classifying 75% of mPDAC and 85% of ICC. Our results suggest that ANXA10 may be useful to differentiate between ICC and mPDAC, when only a tissue specimen is available.

Simvastatin Up-Regulates Annexin A10 That Can Inhibit the Proliferation, Migration, and Invasion in Androgen-Independent Human Prostate Cancer Cells.

BACKGROUND: Statins have recently been studied for their proapoptotic and antimetastatic effects. However, the exact mechanisms of their anticancer actions remain unclear. Using microarrays, we discovered up-regulation of annexin A10 (ANXA10) in PC-3 cells after simvastatin treatment. ANXA10 reportedly has antitumor effects. In this study, we evaluated the effects of simvastatin on ANXA10 signaling in androgen-independent prostate cancer cells. METHODS: PC-3, LNCaP-LA (which were derived from LNCaP cells and cultured in 10% charcoal-stripped fetal bovine serum for 3 months), and DU145 human prostate cancer cell lines were used. Prostate tissues were collected from 60 patients (benign prostatic hyperplasia [BPH], n = 20; prostate cancer with a Gleason score of 7, n = 20; prostate cancer with a Gleason score of 8-10, n = 20) at the time of prostate biopsies performed. We used a nude mouse tumor xenograft model with administration of simvastatin or phosphate-buffered saline via intraperitoneal injection. RESULTS: Simvastatin inhibited the proliferation, migration, and invasion of PC-3, LNCaP-LA, and DU145 cells. The expression level of ANXA10 was up-regulated by simvastatin in PC-3, LNCaP-LA, and DU145 cells. Transfection with ANXA10 inhibited PC-3 and LNCaP-LA cells proliferation, migration, and invasion. Knockdown of ANXA10 by siRNA increased the proliferation of PC-3 and LNCaP-LA cells. In a nude mouse xenograft model of PC-3 cells, simvastatin induced both reduction in the tumor size and up-regulation of ANXA10 expression. In human prostate biopsy samples, ANXA10 mRNA expression was significantly lower in the prostate cancer group than in the BPH group. Next, we found that up-regulation of ANXA10 in PC-3 resulted in down-regulation of S100 calcium binding protein A4 (S100A4), which is reportedly correlated with aggressiveness and a worse prognosis for patients with different types of carcinomas. Expression of S100A4 was down-regulated by simvastatin. In PC-3 cells, knockdown of S100A4 by siRNA inhibited the proliferation, migration, and invasion of PC-3 cells. CONCLUSION: Our results suggest that statins inhibit the proliferation, migration, and invasion of androgen-independent prostate cancer cells by up-regulation of ANXA10. Additionally, it is possible that S100A4 plays a role in these effects. Statins may be beneficial in the prevention and/or treatment of prostate cancer. Prostate 77: 337-349, 2017. © 2016 Wiley Periodicals, Inc.

Comparative Label-Free Mass Spectrometric Analysis of Mildly versus Severely Affected mdx Mouse Skeletal Muscles Identifies Annexin, Lamin, and Vimentin as Universal Dystrophic Markers.

The primary deficiency in the membrane cytoskeletal protein dystrophin results in complex changes in dystrophic muscles. In order to compare the degree of secondary alterations in differently affected subtypes of skeletal muscles, we have conducted a global analysis of proteome-wide changes in various dystrophin-deficient muscles. In contrast to the highly degenerative mdx diaphragm muscle, which showed considerable alterations in 35 distinct proteins, the spectrum of mildly to moderately dystrophic skeletal muscles, including interosseus, flexor digitorum brevis, soleus, and extensor digitorum longus muscle, exhibited a smaller number of changed proteins. Compensatory mechanisms and/or cellular variances may be responsible for differing secondary changes in individual mdx muscles. Label-free mass spectrometry established altered expression levels for diaphragm proteins associated with contraction, energy metabolism, the cytoskeleton, the extracellular matrix and the cellular stress response. Comparative immunoblotting verified the differences in the degree of secondary changes in dystrophin-deficient muscles and showed that the up-regulation of molecular chaperones, the compensatory increase in proteins of the intermediate filaments, the fibrosis-related increase in collagen levels and the pathophysiological decrease in calcium binding proteins is more pronounced in mdx diaphragm as compared to the less severely affected mdx leg muscles. Annexin, lamin, and vimentin were identified as universal dystrophic markers.

Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma.

Annexin A10 (ANXA10) is a member of the ANX family that is normally expressed in gastric mucosa. ANXA10 was recently observed to be upregulated in sessile serrated adenoma, a precursor to microsatellite-unstable colorectal cancer. We investigated the use of ANXA10 in diagnosing colorectal carcinoma. In an immunohistochemical analysis, the intensity and quantity of ANXA10, MUC5AC, MUC6 and CDX2 in 123 colorectal carcinomas were graded. We determined the molecular status of BRAF and KRAS mutations, as well as the microsatellite instability status and the CpG island methylator phenotype in all colorectal carcinomas, and subcategorized into four molecular subgroups according to the molecular derangements. Nuclear ANXA10 staining was present in 36 colorectal carcinomas, exhibiting a strong significant association with the BRAF mutation status (P<0.0001) and positive CpG island methylator phenotype (P<0.0001), and a borderline significant association with high levels of microsatellite instability (P=0.072). The ANXA10-positive colorectal carcinomas were frequently positive for MUC5AC and MUC6, and were associated with absent or reduced CDX2 expression (all P<0.0001). According to a classification and regression tree analysis, ANXA10 is a superior marker for the molecular subtyping of colorectal carcinomas and represents a specific marker for colorectal cancers of the serrated pathway. Our results indicated that ANXA10 expression is implicated in gastric programming in serrated-pathway-associated colorectal carcinoma. ANXA10-positive colorectal carcinoma is highly associated with the molecular features of the serrated neoplasia pathway.

Immunohistochemistry for annexin A10 can distinguish sporadic from Lynch syndrome-associated microsatellite-unstable colorectal carcinoma.

Differentiating sporadic microsatellite-unstable colorectal carcinoma due to MLH1 promoter hypermethylation from Lynch syndrome (LS)-associated tumors due to mutations in mismatch-repair proteins is time consuming, cost intensive, and requires advanced laboratory testing. A mutation in BRAF has been shown to be highly specific for sporadic tumors; however, a significant proportion of sporadic microsatellite-unstable tumors lack BRAF mutations. MLH1 promoter methylation analysis is subsequently used to differentiate LS and sporadic tumors, but both tests require specialized laboratories and are costly. Through previous gene expression profiling of serrated polyps, we identified annexin A10 as a protein highly expressed in sessile serrated adenomas/polyps. As these polyps give rise to the majority of sporadic microsatellite-unstable tumors, we evaluated the ability of annexin A10 expression to discriminate between LS and sporadic tumors. A marked increase in annexin A10 mRNA was observed in sporadic microsatellite-unstable tumors compared with LS tumors (378-fold increase, P<0.001). Using immunohistochemistry, annexin A10 was expressed in 23/53 (43%) BRAF-mutated and 9/22 (41%) BRAF wild-type sporadic tumors. In contrast, only 3/56 (5%) LS tumors were positive for annexin A10 (P<0.0001). One patient had a deleterious MSH2 mutation, and another had a variant of uncertain significance in MSH6. These 2 tumors could be easily distinguished from sporadic tumors using mismatch-repair protein immunohistochemistry. Only 1/28 (4%) LS tumors with loss of MLH1 was positive for annexin A10. This patient did not have a deleterious MLH1 mutation but rather germline promoter hypermethylation of MLH1. On the basis of these results, immunohistochemistry for annexin A10 may be a useful marker to distinguish sporadic from LS-associated microsatellite-unstable colon cancer.

Quantitative proteomic analysis identifying three annexins as lymph node metastasis-related proteins in lung adenocarcinoma.

Lymph node status is a strong predictor of outcome for lung adenocarcinoma (AdC) patients. To explore novel potential protein markers for predicting lymph node metastasis of lung AdC, differential proteomic analysis on microdissected cancer cells from primary lung AdC and matched lymph node (LN) metastatic tissues by laser capture microdissection (LCM) was conducted using two-dimensional differential in-gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Annexins including annexin-1, annexin-2 and annexin-3 were identified and found to be overexpressed in matched LN metastatic tissues compared to primary lung AdC. Furthermore, differential expression levels of the three annexins were evaluated in paraffin-embedded 188 primary lung AdC tissues and 65 matched positive lymph node specimens using immunohistochemistry. High expression of annexin-1, annexin-2, and annexin-3 was all frequently observed in matched positive lymph node tissues compared to primary lung AdC. In primary lung AdC, expression levels of the three annexins in primary lymph node-positive AdC tissues were higher than primary lymph node-negative AdC tissues. Multivariate logistic regression analysis indicated annexin-1, annexin-2, and annexin-3 were all significant risk factors for lymph node metastasis. Furthermore, statistical analysis indicated that the concomitant expression of annexin-1/annexin-2, annexin-1/annexin-3, or annexin-2/annexin-3 and combined expression of all three markers had stronger correlation with lymph node metastasis. Our results suggest that annexin-1, annexin-2, and annexin-3 are identified as potential biomarkers associated with lymph node metastasis in lung AdC.

Whole cigarette smoke promotes human gingival epithelial cell apoptosis and inhibits cell repair processes.

BACKGROUND AND OBJECTIVE: Smoking cigarettes increases the risk of developing various types of human diseases, including cancers and periodontitis. As gingival epithelial cells are known to play an active role in innate immunity via the secretion of a wide variety of mediators, and as these cells are the first ones exposed to environmental stimuli such as cigarette smoke, we sought to investigate the effects of whole cigarette smoke on normal human gingival epithelial cells and tissue. MATERIAL AND METHODS: Human gingival epithelial cells were extracted from healthy nonsmokers and used either as a monolayer or as an engineered human oral mucosa to investigate the effect of whole cigarette smoke on cell growth, apoptosis and wound repair/migration. RESULTS: Our findings show that when gingival epithelial cells were exposed once to whole cigarette smoke, this resulted in a significant inhibition of cell growth through an apoptotic pathway, as confirmed by an increase of Bax and a decrease of Bcl-xL and caspase-3 activity. Cigarette smoke also inhibited epithelial cell migration. These effects may explain the disorganization of the engineered human oral mucosa tissue when exposed to whole cigarette smoke. CONCLUSION: Exposure to whole cigarette smoke markedly inhibits epithelial cell growth through an apoptosis/necrosis pathway that involves Bax and Bcl-xL proteins and caspase-3 activity. Cigarette smoke also disrupts epithelial cell migration, which may negatively affect periodontal wound healing.

Biological modulation by lectins and their ligands in tumor progression and metastasis.

Lectins are a group of specific proteins that preferentially bind to carbohydrates inside and outside cells. To date, an increasing number of animal lectins have been found and categorized into several families in terms of the significant primary structural homology, while the classification is not always straightforward. These lectins can exert immense biological functions mainly through their specific carbohydrate-protein interactions in a variety of situations. In cancer biology, aberrant glycosylation changes on many glycoproteins and glycolipids are often observed and numerous experimental evidences have revealed that these structural changes are related to tumor malignancy. Galectins, which are broadly expressed animal lectins, can play crucial biological roles in tumor cell-cell or cell-matrix interactions through their binding activities to the tumor cell surface carbohydrate determinants. Certain galectin family proteins have also shown to affect tumor cell survival, signal transduction, and proliferation mainly inside the cell. Selectins, which are one of the C-type lectins and expressed leukocytes and/or vascular endothelium, can also play an immense role in tumor cell adhesion and invasion. In addition, certain annexin family proteins, which are originally known as phospholipid binding proteins, have been revealed to possess the carbohydrate binding activity, and these novel functions in tumors are being unveiled. Understanding how carbohydrate-protein interactions function in tumor cells will be one of the important goals in cancer research. This review focuses on the role of these lectins and their ligands in cancer progression and metastasis.

Inhibition of adenosine monophosphate-activated protein kinase induces apoptosis in multiple myeloma cells.

In this study, we show that adenosine monophosphate-activated protein kinase (AMPK) is expressed and activated in multiple myeloma cells. The inhibition of AMPK induced growth arrest and reduction of cell viability in the cell viability assay using the water-soluble tetrazolium salt 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1 assay). Induction of apoptosis was determined by annexin-V and propidium iodide staining. The prevention of apoptosis using the pancaspase inhibitor ZVAD-fmk and caspase-3 cleavage upon incubation with the AMPK inhibitor (AMPKI) is shown. Furthermore, incubation of myeloma cells with AMPKI resulted in the downregulation of pAMPK, Mcl-1 and Bcl-xL. Coincubation of AMPKI and melphalan led to a strong additional increase of apoptosis in myeloma cells. We conclude that AMPKI has a strong antimyeloma activity in vitro and represents a new targeted strategy in the treatment of multiple myeloma.

Annexinopathies.

Annexins comprise a conserved family of proteins characterised by their ability to bind and order charged phospholipids in membranes, often in response to elevated intracellular calcium. The family members (there are at least 12 in humans) have become specialised over evolutionary time and are involved in a diverse range of cellular functions both inside the cell and extracellularly Although a mutation in an annexin has never been categorically proven to be the cause of a disease state, they have been implicated in pathologies as diverse as autoimmunity, infection, heart disease, diabetes and cancer. 'Annexinopathies' were first described by Jacob H. Rand to describe the pathological sequelae in two disease states, the overexpression of annexin 2 in a patients with a haemorrhagic form of acute promyelocytic leukaemia, and the under-expression of annexin 5 on placental trophoblasts in the antiphospholipid syndrome. In this chapter we will outline some of the more recent observations in regard to these conditions, and describe the involvement of annexins in some other major causes of human morbidity.

Ligand-binding activity and expression profile of annexins in Caenorhabditis elegans.

Mammalian annexins are implicated in several physiological mechanisms based on their calcium-dependent phospholipid/membrane binding and carbohydrate-binding activities. In this study, we investigated gene expression profiles of all four Caenorhabditis elegans annexins, nex-1, -2, -3 and -4, throughout the development, and compared phospholipid- and carbohydrate-binding properties of their protein products, NEX-1, -2, -3 and -4. We found that nex-1 and -3 are transcribed continuously during the developmental stages, while expression of nex-2 and -4 appeared to be temporal, peaking at the L1 stage followed by a gradual decrease toward the adult stage. NEX-1 and -3 were detected as single protein band in total worm extracts by immunoblotting, but NEX-2 was heterogenic in size. NEX-1, -2, and -3 showed the binding activities to phosphatidylserine, phosphatidylinositol and phosphatidylethanolamine, but not to phosphatidylcholine. In contrast to their uniform phospholipids-binding properties, their glycosaminoglycan-binding activities were distinctive. NEX-2 bound to heparan sulfate and chondroitin, NEX-3 bound only to heparan sulfate, and NEX-1 showed no lectin activities under tested conditions. NEX-4 had neither phospholipids- nor carbohydrate-binding properties. Differentiated expression profiles and ligand-binding properties of NEX-1, -2, -3 and -4, shown in our study, may represent distinctive roles for each C. elegans annexins.

Molecular characterization and anticoagulant activity of a novel annexin derived from the Taenia solium.

A novel annexin gene was isolated from the Taenia solium cDNA library by degenerate PCR. The purified protein was generated by hydrolysis with thrombin in glutathione S-transferase (GST) affinity chromatography following expression in GST tagged pGEX-5T vector. It shares the common structural features of the annexin family and specially possesses two unique fragments between repeating domains II and III which do not exist in other annexin family members revealed by aligning and homology modeling, hence it was designated as Tso ANXB2 according to the new nomenclature of annexins. According to the parasitic behaviors of the origin, a series of coagulation assays was performed, indicating that Tso ANXB2 inhibits extrinsic blood coagulation pathway and platelet aggregation also has platelet binding activity. Nevertheless, the mutant protein deleting the consensus coagulation-related KGD motif of Tso ANXB2 showed significant decreasing platelet binding and anticoagulation activity.

Developmental profile of annexin IX and its possible role in programmed cell death of the Bombyx mori anterior silk gland.

During pupal metamorphosis, the anterior silk gland (ASG) of the silkworm, Bombyx mori, undergoes programmed cell death (PCD), which is triggered by 20-hydroxyecdysone (20E). Annexin IX (ANX IX) has been identified as a 20E-inducible gene in dying ASGs, and we show here that its expression is down-regulated in tissues destined to die but not in tissues that survive pupal metamorphosis. ANX IX expression was high in the ASGs during the feeding period, when the ecdysteroid titer was low, and decreased in response to the rising ecdysteroid titer that triggered pupal metamorphosis. Before gut purge, in vitro exposure of the ASGs to 20E levels corresponding to the ecdysteroid concentration present at the time of gut purge caused a decrease in ANX IX messenger RNA levels. Expression profiles of EcR and USP, and the 20E concentration-responses of these genes, indicate the importance of the relative abundance of EcR-A and EcR-B1 isoforms in ANX IX regulation. These results suggest an involvement of ANX IX in the determination of PCD timing by delaying or suppressing the response to the increase in hemolymph ecdysteroid concentration during the prepupal period.

Expression and functions of annexins in the kidney.

This review article summarizes current knowledge about the locations and possible functions of annexin family members in the kidney. Beginning with an introduction on common structural and biochemical features as well as general functional characteristics of annexins, the paper focuses on individual members with documented and/or proposed physiological relevance for renal development, structure, and functions. Three main aspects of annexin function in kidney epithelia emerge from the available experimental data. First, annexins are required for membrane organization and membrane transport events required for the establishment/maintenance of epithelial polarity. Second, there is accumulating evidence of an association of annexins with ion channels, as membrane-guiding auxiliary proteins or modulators of channel activity. Last but not least, some annexins seem to work as extracellular autocrine modulators of receptor function under different physiological conditions.