Could Gas6/TAM Axis Provide Valuable Insights into the Pathogenesis of Systemic Sclerosis?
Abstract
1. Introduction
1.1. Clinical Manifestation of SSc
1.2. Complications of SSc
1.3. Pathogenesis of SSc
1.3.1. Vascular Injury
1.3.2. Inflammation
1.3.3. Activation of Fibroblasts
1.3.4. Autoantibodies in SSc
2. Gas6/TAM System
2.1. Gas6/TAM System’s Functions
2.2. Gas6/TAM System in Human Diseases
2.2.1. Gas6/TAM in Cancer
2.2.2. Gas6/TAM System in Liver Diseases
2.2.3. Gas6/TAM System in Lung Diseases
2.2.4. Gas6/TAM System in Infectious Diseases
2.2.5. Gas6/TAM System in Cardiovascular Diseases
2.2.6. Gas6/TAM System in Rheumatic Diseases
2.3. Gas6/TAM System in Systemic Sclerosis
3. Treatment of SSc
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Autoantibodies | Phenotypes | Target | Clinical Associations |
---|---|---|---|
ACA | lcSSc | ACA are mainly directed towards three centromere proteins, namely CENP-A, B, and C. | Cutaneous calcinosis, dermal thickness of hands and/or feet distally from elbow and knee, respectively, and PAH. |
Anti-topo I | dcSSc | Anti-topo I are directed towards a nuclear protein of 70–100 kD, clustered with DNA molecules and involved in altering DNA chain conformation during cellular replication. | Ischemic digital ulcers, flexion contractures in metacarpophalangeal and proximal interphalangeal joints, hand disability, and progressive pulmonary fibrosis. |
Anti-RNA pol III | dcSSc | Anti-RNA pol III antibodies are reactive with RNA polymerase III. | Joint contractures, scleroderma renal crisis |
Anti-Th/To | lcSSc | Anti-Th/To are directed towards protein components of the RNase MRP complex. | ILD and pericarditis. |
Treatments | Effects | Involvement in Other Conditions | Possible Involvement of Gas6/TAM Axis | References |
---|---|---|---|---|
TOC and RTX, bDMARDs | TOC: Inhibition of the IL-6-mediated signaling pathways, leading to a reduction in inflammation and immune response modulation.RTX: Depletion of B cells. | Proven. | Increased expression of Axl and MerTK in the RA synovial tissue, suggesting that IL-6 inhibition may exert part of its anti-inflammatory effects through upregulation of TAM receptors. | [152] |
Prednisolone, glucocorticoids | Anti-inflammatory and immunosuppressive properties. | Proven. | Glucocorticoids can upregulate the expression of MerTK enhancing the clearance of apoptotic cells and promoting anti-inflammatory pathway. | [160,161] |
Nintedanib, tyrosine kinase inhibitor | It targets multiple tyrosine kinases involved in the processes of fibrosis, inflammation, and vascular remodeling. | Proven. | Gas6/TAM receptor activity contributes to the activation of pulmonary fibroblasts in IPF and targeting of TAM receptors alleviates fibrotic mechanisms. | [131] |
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Apostolo, D.; D’Onghia, D.; Nerviani, A.; Ghirardi, G.M.; Sola, D.; Perazzi, M.; Tonello, S.; Colangelo, D.; Sainaghi, P.P.; Bellan, M. Could Gas6/TAM Axis Provide Valuable Insights into the Pathogenesis of Systemic Sclerosis? Curr. Issues Mol. Biol. 2024, 46, 7486-7504. https://doi.org/10.3390/cimb46070444
Apostolo D, D’Onghia D, Nerviani A, Ghirardi GM, Sola D, Perazzi M, Tonello S, Colangelo D, Sainaghi PP, Bellan M. Could Gas6/TAM Axis Provide Valuable Insights into the Pathogenesis of Systemic Sclerosis? Current Issues in Molecular Biology. 2024; 46(7):7486-7504. https://doi.org/10.3390/cimb46070444
Chicago/Turabian StyleApostolo, Daria, Davide D’Onghia, Alessandra Nerviani, Giulia Maria Ghirardi, Daniele Sola, Mattia Perazzi, Stelvio Tonello, Donato Colangelo, Pier Paolo Sainaghi, and Mattia Bellan. 2024. "Could Gas6/TAM Axis Provide Valuable Insights into the Pathogenesis of Systemic Sclerosis?" Current Issues in Molecular Biology 46, no. 7: 7486-7504. https://doi.org/10.3390/cimb46070444
APA StyleApostolo, D., D’Onghia, D., Nerviani, A., Ghirardi, G. M., Sola, D., Perazzi, M., Tonello, S., Colangelo, D., Sainaghi, P. P., & Bellan, M. (2024). Could Gas6/TAM Axis Provide Valuable Insights into the Pathogenesis of Systemic Sclerosis? Current Issues in Molecular Biology, 46(7), 7486-7504. https://doi.org/10.3390/cimb46070444