Dataset Information

The Cardiac Syndecan-2 Interactome.

ABSTRACT: The extracellular matrix (ECM) is important in cardiac remodeling and syndecans have gained increased interest in this process due to their ability to convert changes in the ECM to cell signaling. In particular, syndecan-4 has been shown to be important for cardiac remodeling, whereas the role of its close relative syndecan-2 is largely unknown in the heart. To get more insight into the role of syndecan-2, we here sought to identify interaction partners of syndecan-2 in rat left ventricle. By using three different affinity purification methods combined with mass spectrometry (MS) analysis, we identified 30 novel partners and 9 partners previously described in the literature, which together make up the first cardiac syndecan-2 interactome. Eleven of the novel partners were also verified in HEK293 cells (i.e., AP2A2, CAVIN2, DDX19A, EIF4E, JPH2, MYL12A, NSF, PFDN2, PSMC5, PSMD11, and RRAD). The cardiac syndecan-2 interactome partners formed connections to each other and grouped into clusters mainly involved in cytoskeletal remodeling and protein metabolism, but also into a cluster consisting of a family of novel syndecan-2 interaction partners, the CAVINs. MS analyses revealed that although syndecan-2 was significantly enriched in fibroblast fractions, most of its partners were present in both cardiomyocytes and fibroblasts. Finally, a comparison of the cardiac syndecan-2 and -4 interactomes revealed surprisingly few protein partners in common.

SUBMITTER: Mathiesen SB

PROVIDER: S-EPMC7483480 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Cardiac Syndecan-2 Interactome.

Mathiesen Sabrina Bech SB Lunde Marianne M Stensland Maria M Martinsen Marita M Nyman Tuula A TA Christensen Geir G Carlson Cathrine Rein CR

Frontiers in cell and developmental biology 20200828

The extracellular matrix (ECM) is important in cardiac remodeling and syndecans have gained increased interest in this process due to their ability to convert changes in the ECM to cell signaling. In particular, syndecan-4 has been shown to be important for cardiac remodeling, whereas the role of its close relative syndecan-2 is largely unknown in the heart. To get more insight into the role of syndecan-2, we here sought to identify interaction partners of syndecan-2 in rat left ventricle. By us ...[more]

PMID: 32984315

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Project description:Background: Acute kidney injury (AKI) is a common complication after cardiac surgery and the prognosis of AKI worsens with the increase in AKI severity. Syndecan-1(SDC-1) is a biomarker of endothelial glycocalyx degradation. Fluid overload (FO) is associated with poor outcomes in AKI patients and may be related to the damage of endothelial function. This study aimed at demonstrating the association between elevated SDC-1, FO, and AKI progression. Methods: In this prospective study, we screened patients who underwent cardiac surgery and enrolled patients who experienced an AKI within 48 h after surgery from December 1, 2018 to January 31, 2019. Blood and urine samples were collected at the time of AKI diagnosis for plasma SDC-1 (pSDC-1) and urine SDC-1 (uSDC-1) measurements. Fluid balance (FB) = accumulated [fluid intake (L) - fluid output (L)]/body weight (kg) × 100%. FO was defined as FB > 5%. The primary endpoint was progressive AKI, defined as AKI progression from a lower to a higher stage. The patients were divided into progressive AKI group vs. non-progressive AKI group. Results: The quartiles of pSDC-1 concentration (117.3 [67.4, 242.3] ng/mL) showed a graded association with the incidence of progressive AKI, ranging from 5.0, 11.9, 32.6 to 52.4% (p for trend < 0.001). Multivariate logistic regression showed that increased pSDC-1 was an independent risk factor for progressive AKI. The AUC-ROC area of pSDC-1 concentration in predicting AKI progression was 0.847. Linear regression showed a positive correlation between FB and pSDC-1 concentration (R 2 = 0.384, p < 0.001). In patients with FO, the progressive AKI incidence was significantly higher in the high pSDC-1 (≥117.3 ng/mL) subgroup than in the low pSDC-1 subgroup (58.3 vs. 17.6%, OR = 9.167, P = 0.005). In patients without FO, the progressive AKI incidence was also significantly higher in the high pSDC-1 subgroup with a lower odds ratio (30.4 vs. 7.4%, OR = 6.714, P = 0.002). Conclusion: Elevated pSDC-1 concentration was associated with progressive AKI after cardiac surgery and showed good predictive ability for progressive AKI. FB was related to the increase of pSDC-1. The interaction between pSDC-1 and FB may further aggravate the progression of AKI.

Project description:Small Heat Shock Proteins (sHSPs) are molecular chaperones that transiently interact with other proteins, thereby assisting with quality control of proper protein folding and/or degradation. They are also recruited to protect cells from a variety of stresses in response to extreme heat, heavy metals, and oxidative-reductive stress. Although ten human sHSPs have been identified, their likely diverse biological functions remain an enigma in health and disease, and much less is known about non-redundant roles in selective cells and tissues. Herein, we set out to comprehensively characterize the cardiac-restricted Heat Shock Protein B-2 (HspB2), which exhibited ischemic cardioprotection in transgenic overexpressing mice including reduced infarct size and maintenance of ATP levels. Global yeast two-hybrid analysis using HspB2 (bait) and a human cardiac library (prey) coupled with co-immunoprecipitation studies for mitochondrial target validation revealed the first HspB2 "cardiac interactome" to contain many myofibril and mitochondrial-binding partners consistent with the overexpression phenotype. This interactome has been submitted to the Biological General Repository for Interaction Datasets (BioGRID). A related sHSP chaperone HspB5 had only partially overlapping binding partners, supporting specificity of the interactome as well as non-redundant roles reported for these sHSPs. Evidence that the cardiac yeast two-hybrid HspB2 interactome targets resident mitochondrial client proteins is consistent with the role of HspB2 in maintaining ATP levels and suggests new chaperone-dependent functions for metabolic homeostasis. One of the HspB2 targets, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), has reported roles in HspB2 associated phenotypes including cardiac ATP production, mitochondrial function, and apoptosis, and was validated as a potential client protein of HspB2 through chaperone assays. From the clientele and phenotypes identified herein, it is tempting to speculate that small molecule activators of HspB2 might be deployed to mitigate mitochondrial related diseases such as cardiomyopathy and neurodegenerative disease.

Dataset Information

The Cardiac Syndecan-2 Interactome.

Publications

The Cardiac Syndecan-2 Interactome.

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