Integrative view of serpins in health and disease: the contribution of serpinA3

Sánchez‐Navarro, Andrea; González-Soria, Isaac; Caldiño‐Bohn, Rebecca I.; Bobadilla, Norma A.

doi:10.1152/ajpcell.00366.2020

Cited by 74 publications

(81 citation statements)

References 6 publications

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“…The co-regulation of these proteins may suggest the involvement of certain pathways in the association of diabetes with severe obesity. The primary target of SERPINA1 is elastase, but it also has a moderate affinity for plasmin and thrombin [42]. An imbalance between SERPINA1 and neutrophil elastase might contribute to the development of obesity and related inflammation, insulin resistance, and liver steatosis [43].…”

Section: Discussionmentioning

confidence: 99%

Remission of Diabetes Following Bariatric Surgery: Plasma Proteomic Profiles

Insenser

Vilarrasa

Vendrell

et al. 2021

JCM

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Bariatric surgery restores glucose tolerance in many, but not all, severely obese subjects with type 2 diabetes (T2D). We aimed to evaluate the plasma protein profiles associated with the T2D remission after obesity surgery. We recruited seventeen women with severe obesity submitted to bariatric procedures, including six non-diabetic patients and eleven patients with T2D. After surgery, diabetes remitted in 7 of the 11 patients with T2D. Plasma protein profiles at baseline and 6 months after bariatric surgery were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight coupled to mass spectrometry (MALDI-TOF/TOF MS). Remission of T2D following bariatric procedures was associated with changes in alpha-1-antichymotrypsin (SERPINA 3, p < 0.05), alpha-2-macroglobulin (A2M, p < 0.005), ceruloplasmin (CP, p < 0.05), fibrinogen beta chain (FBG, p < 0.05), fibrinogen gamma chain (FGG, p < 0.05), gelsolin (GSN, p < 0.05), prothrombin (F2, p < 0.05), and serum amyloid p-component (APCS, p < 0.05). The resolution of diabetes after bariatric surgery is associated with specific changes in the plasma proteomic profiles of proteins involved in acute-phase response, fibrinolysis, platelet degranulation, and blood coagulation, providing a pathophysiological basis for the study of their potential use as biomarkers of the surgical remission of T2D in a larger series of severely obese patients.

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Section: Discussionmentioning

confidence: 99%

Remission of Diabetes Following Bariatric Surgery: Plasma Proteomic Profiles

Insenser

Vilarrasa

Vendrell

et al. 2021

JCM

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“…As for the source of SERPINA3, on the one hand, SERPINA3 is secreted by the liver as reported in previous studies (13), because the atherosclerosis occurrence is often accompanied by systemic changes and is correlated with metabolic liver diseases through multiple pathophysiological mechanisms (26,27). On the other hand, existing data showed an increased expression of SERPINA3 in atherosclerotic lesions from a minor stroke and TIA, and SERPINA3 mRNA level was higher in plaque aorta of Apoe −/− mice than in plaque-free aorta of control mice (16).…”

Section: Discussionmentioning

confidence: 93%

“…Serine proteinase inhibitor A3 (SERPINA3), also named antichymotrypsin (ACT), is another member of the Serpin superfamily. Several serine proteases, such as leukocyte cathepsin G, mast cell chymases, pancreatic chymotrypsin, and lung serum protease, are inhibited by SERPINA3 ( 13 ). Moreover, cathepsin G expressed in neutrophil granules and secreted by inflammation is the primary target for SERPINA3 ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease

Lei

et al. 2021

Front. Cardiovasc. Med.

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Background: Serine proteinase inhibitor A3 (SERPINA3) has been discovered in the pathogenesis of many human diseases, but little is known about the role of SERPINA3 in coronary artery disease (CAD). Therefore, we aim to determine its relationship with CAD and its function in the pathogenesis of atherosclerosis.Methods: In total 86 patients with CAD and 64 patients with non-CAD were compared. The plasma SERPINA3 levels were measured using ELISA. Logistic regression analysis and receiver-operating characteristic (ROC) analysis were performed to illustrate the association between plasma SERPINA3 levels and CAD. In vitro, real-time PCR (RT-PCR) and immunofluorescence staining were used to determine the expression of SERPINA3 in atherosclerotic plaques and their component cells. Then rat aortic smooth muscle cells (RASMCs) were transfected with siRNA to knock down the expression of SERPINA3 and human umbilical vein endothelial cells (HUVECs) were stimulated by SERPINA3 protein. EdU assay and scratch assay were used for assessing the capability of proliferation and migration. The cell signaling pathway was evaluated by western blot and RT-PCR.Results: Patients with CAD [104.4(54.5–259.2) μg/mL] had higher levels of plasma SERPINA3 than non-CAD [65.3(47.5–137.3) μg/mL] (P = 0.004). After being fully adjusted, both log-transformed and tertiles of plasma SERPINA3 levels were significantly associated with CAD. While its diagnostic value was relatively low since the area under the ROC curve was 0.64 (95% CI: 0.55–0.73). Secreted SERPINA3 might increase the expression of inflammatory factors in HUVECs. Vascular smooth muscle cells had the highest SERPINA3 expression among the aorta compared to endothelial cells and inflammatory cells. The knockdown of SERPINA3 in RASMCs attenuated its proliferation and migration. The phosphorylated IκBα and its downstream pathway were inhibited when SERPINA3 was knocked down.Conclusions: Elevated plasma SERPINA3 levels were associated with CAD. SERPINA3 can increase inflammatory factors expression in HUVECs. It can regulate VSMCs proliferation, migration, and releasing of inflammatory factors through the NF-κB signaling pathway. Thus, SERPINA3 played a significant role in the pathogenesis of atherosclerosis.

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“…Serine protease inhibitors (serpins) comprise the most widely distributed superfamily of protease inhibitors, and their anti-inflammatory properties have been demonstrated in inflammatory disorders [ 11 , 12 , 13 ]. Over the past few decades, the attention of the medical and research community has been focused on host serpins for disease management.…”

Section: Introductionmentioning

confidence: 99%

Gut Serpinome: Emerging Evidence in IBD

Mkaouar

Mariaule

Rhimi

et al. 2021

IJMS

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Inflammatory bowel diseases (IBD) are incurable disorders whose prevalence and global socioeconomic impact are increasing. While the role of host genetics and immunity is well documented, that of gut microbiota dysbiosis is increasingly being studied. However, the molecular basis of the dialogue between the gut microbiota and the host remains poorly understood. Increased activity of serine proteases is demonstrated in IBD patients and may contribute to the onset and the maintenance of the disease. The intestinal proteolytic balance is the result of an equilibrium between the proteases and their corresponding inhibitors. Interestingly, the serine protease inhibitors (serpins) encoded by the host are well reported; in contrast, those from the gut microbiota remain poorly studied. In this review, we provide a concise analysis of the roles of serine protease in IBD physiopathology and we focus on the serpins from the gut microbiota (gut serpinome) and their relevance as a promising therapeutic approach.

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Integrative view of serpins in health and disease: the contribution of serpinA3

Cited by 74 publications

References 6 publications

Remission of Diabetes Following Bariatric Surgery: Plasma Proteomic Profiles

Remission of Diabetes Following Bariatric Surgery: Plasma Proteomic Profiles

The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease

Gut Serpinome: Emerging Evidence in IBD

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