The Gas6/TAM System and Multiple Sclerosis

Bellan, Mattia; Pirisi, Mario; Sainaghi, Pier Paolo

doi:10.3390/ijms17111807

Cited by 42 publications

(34 citation statements)

References 109 publications

(136 reference statements)

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“…On these premises, Gas6 and TAM have been found to be related to rheumatoid arthritis, 33 connective tissue diseases, 34 , 35 Alzheimer’s disease 36 and multiple sclerosis. 37 Furthermore, TAM are involved in hemostasis, also being receptors of protein S, a master regulator of the coagulative cascade; Gas6 seems to play a complementary role in platelet function 38 and it has been proposed as a biomarker for the diagnosis of pulmonary embolism. 39 …”

Section: Growth Arrest-specific 6 (Gas6)mentioning

confidence: 99%

Candidate Biomarkers of Liver Fibrosis: A Concise, Pathophysiology-oriented Review

Bellan¹,

Castello²,

Pirisi³

2018

Journal of Clinical and Translational Hepatology

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Repair of sustained liver injury results in fibrosis (i.e. the accumulation of extracellular matrix proteins), and ultimately the complete distortion of parenchymal architecture of the liver, which we call cirrhosis. Detecting and staging of fibrosis is thus a mainstay in the management of chronic liver diseases, since many clinically relevant decisions, such as starting treatment and/or monitoring for complications including hepatocellular carcinoma, may depend on it. The gold standard for fibrosis staging is liver biopsy, the role of which, however, is questioned nowadays because of cost, hazards and poor acceptance by patients. On the other hand, imaging techniques and/or measurement of direct and indirect serum markers have not proved to be completely satisfactory under all circumstances as alternatives to liver biopsy. Making progress in this field is now more crucial than ever, since treatments for established fibrosis appear on the horizon. Fine dissection of the pathways involved in the pathophysiology of liver diseases has put forward several novel candidate biomarkers of liver fibrosis, such as growth arrest-specific6, Mac-2-binding protein, osteopontin, placental growth factor, growth/differentiation factor 15 and hepatocyte growth factor. All molecules have been suggested to have potential to complement or substitute methods currently used to stage liver diseases. Here, we review the pros and cons for their use in this setting.

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Section: Growth Arrest-specific 6 (Gas6)mentioning

confidence: 99%

Candidate Biomarkers of Liver Fibrosis: A Concise, Pathophysiology-oriented Review

Bellan¹,

Castello²,

Pirisi³

2018

Journal of Clinical and Translational Hepatology

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“…It also plays a role in clearing cellular and myelin debris from inflammatory demyelination. This is an important initial step to recover myelin fibers [ 100 ]. Additionally, the Gas6/TAM complex promotes survival of neuron and glial cell in the CNS, contributing to the process of myelination [ 100 ].…”

Section: Tam Receptors and Autoimmune Diseasesmentioning

confidence: 99%

“…Cuprizone (bis-cyclohexanone-oxaldihydrazone)-treated mice are used as a model to study MS. Cuprizone causes toxic demyelination without altering the blood/brain barrier. In cuprizone damaged tissue, oligodendrocytes and microglial/macrophages fail to accumulate [ 100 , 101 , 102 ]. In mice, cuprizone treatment results in decreased Tyro3 and increased Gas6 , Axl , and Mer transcription [ 100 , 103 ].…”

Section: Tam Receptors and Autoimmune Diseasesmentioning

confidence: 99%

“…In cuprizone damaged tissue, oligodendrocytes and microglial/macrophages fail to accumulate [ 100 , 101 , 102 ]. In mice, cuprizone treatment results in decreased Tyro3 and increased Gas6 , Axl , and Mer transcription [ 100 , 103 ]. More severe demyelination, a greater reduction in oligodendrocyte number, and an overactivation of microglia was found in mice lacking Gas6 [ 103 ].…”

Section: Tam Receptors and Autoimmune Diseasesmentioning

confidence: 99%

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The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview

Wium

Paccez

Zerbini

2018

Cells

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Receptor tyrosine kinases (RTKs) regulate cellular processes by converting signals from the extracellular environment to the cytoplasm and nucleus. Tyro3, Axl, and Mer (TAM) receptors form an RTK family that plays an intricate role in tissue maintenance, phagocytosis, and inflammation as well as cell proliferation, survival, migration, and development. Defects in TAM signaling are associated with numerous autoimmune diseases and different types of cancers. Here, we review the structure of TAM receptors, their ligands, and their biological functions. We discuss the role of TAM receptors and soluble circulating TAM receptors in the autoimmune diseases systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Lastly, we discuss the effect of TAM receptor deregulation in cancer and explore the therapeutic potential of TAM receptors in the treatment of diseases.

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“…These soluble forms are the result of the proteolytic cleavage by two metalloproteinases, ADAMTS 17 and ADMATS 10, and probably act as decoy receptors for the ligands [13,15]. The Gas6/TAM system is highly pleiotropic and involved in several functions: among them, it seems to have a relevant role in the regulation of inflammatory response [16,17], tissue repair and fibrosis development [14], and vascular integrity [18,19]. Consistently, an impairment of the Gas6/-TAM system has been associated with the development of autoimmune diseases, as demonstrated by the murine model of triple knock-out for the TAM receptors [20].…”

Section: Introductionmentioning

confidence: 99%

Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders

et al. 2020

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Background. Few biomarkers are available for early identification of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) in systemic sclerosis (SS) and scleroderma spectrum disorders (SSD). Aims. To evaluate Gas6, sAxl, and sMer as biomarkers for cardiopulmonary complications of SS and SSD. Methods. In a cross-sectional observational study, we recruited 125 consecutive patients, affected by SS and SSD and referred to a tertiary-level pulmonary hypertension outpatient clinic. All patients underwent a comprehensive evaluation for identification of PAH and ILD. Gas6, sMer, and sAxl concentrations were measured with ELISA protocols, and concentrations were compared according to PAH or ILD. Results. Nineteen subjects had pulmonary hypertension (PH) (14 PAH), and 39 had ILD (6 severe). Plasma sMer was increased in PAH (18.6 ng/ml IQR [11.7-20.3]) with respect to the absence (12.4 [8.0-15.8]) or other form of pulmonary hypertension (9.6 [7.4-12.5]; K–W variance p<0.04). Conversely, Gas6 and sAxl levels were slightly increased in mild ILD (25.8 ng/ml [19.5-32.1] and 24.6 [20.1-32.5]) and reduced in severe ILD (16.6 [15.0-22.1] and 15.5 [14.9-22.4]) in comparison to no evidence of ILD (23.4 [18.8-28.1] and 21.6 [18.1-28.4]; K–W, p≤0.05). Plasma sMer≥19 ng/ml has 50% sensitivity and 92% specificity in PAH identification (area under the ROC curve (AUC) 0.697, p<0.03). Values of Gas6≤24.5 ng/ml and of sAxl≤15.5 ng/ml have 100% and 67% sensitivity and 47% and 86% specificity, respectively, in identifying severe ILD (Gas6 AUC 0.787, p<0.001; sAxl AUC 0.705, p<0.05). Conclusions. The assay of Gas6 sAxl and sMer may be useful to help in the identification of PAH and ILD in SS and SSD patients. The Gas6/TAM system seems to be relevant in cardiopulmonary complications of SS and SSD and merits further investigations.

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The Gas6/TAM System and Multiple Sclerosis

Cited by 42 publications

References 109 publications

Candidate Biomarkers of Liver Fibrosis: A Concise, Pathophysiology-oriented Review

Candidate Biomarkers of Liver Fibrosis: A Concise, Pathophysiology-oriented Review

The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview

Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders

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