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The Serum Amyloid A (SAA) Family: (Patho)Physiological Functions in (Non)Mammalian Systems

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 30 December 2024 | Viewed by 2453

Special Issue Editors


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Guest Editor
Guest Scientist, Division of Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6, Bauteil K, 4. OG, 8010 Graz, Austria
Interests: antioxidants; atherosclerosis, acute-phase reaction; inflammation; native and modified (lipo)proteins; mammalian peroxidases; oxidative modifications; Serum Amyloid A (SAA)
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Guest Editor
Maisonneuve-Rosemont Hospital, Department of Pathology and Cell Biology, University of Montreal, Montreal, QC H1T 2M4, Canada
Interests: innate immunity; inflammation/resolution of inflammation; acute-phase proteins; leukocyte biology; cardiovascular diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Serum Amyloid A (SAA) family is commonly considered an evolutionary old and highly conserved family consisting of basically four different proteins (SAA1–SAA4) encoded by four different genes (SAA1SAA4 or Saa1Saa4) in the mammalian system. SAA1 and SAA2 (commonly termed acute-phase SAA [A-SAA]) share high homology on DNA/RNA (including various allelic variations) and on a protein level, which were originally considered to be only of hepatic origin. From a classical point of view, their major functions were previously considered to be as follows: (i) as precursor proteins of secondary reactive amyloidosis (forming amyloid fibrils), (ii) as classical acute-phase reactants, and (iii) as major protein moiety of high-density lipoproteins during inflammation. However, ongoing studies have revealed the extrahepatic expression of non-glycosylated A-SAA proteins, which may act locally and serve as potential biomarkers in chronic diseases, including different types of cancer, chronic obstructive pulmonary disease, atherosclerosis, innate immunity, and others.

Despite the fact that, in humans, SAA3 has been definitively confirmed to be a pseudogene, while SAA3 proteins of other mammalian species may well be considered as potent acute-phase reactants with yet widely unidentified functions. In particular, sexually dimorphic relationships among Saa3, inflammation, and cholesterol metabolism have been reported to modulate atherosclerosis in the murine system.

In contrast to mammalian SAA1/2 proteins, glycosylated SAA4 (which, in principle, is not prone to form amyloid A fibrils) is not considered a major acute-phase reactant. Therefore, it is termed as constitutively expressed SAA [C-SAA], although it shares striking homology with SAA1/2 in the N-terminal portion. SAA4 is abundantly expressed in humans and mice, although its function is largely unknown. Surprisingly, rats, the only mammalian species thus far that has been identified to not express A-SAA on a protein level, are prone to expressing SAA4.

Therefore, the main focus of this Special Issue will be the expression and roles of different (non)mammalian SAA1–4 mRNAs and proteins in (patho)physiological conditions, their potential activities in promoting disease progression, and their use as potential targets for therapy. In particular, clinical studies, as well as preclinical models with SAA-knock-out, double knock-out or even knock-in models, should be considered to shed light on the adverse or beneficial effects of SAA both in human pathologies and other (non)mammalian species.

We cordially invite you to contribute to this Special Issue with original research articles, brief communications, or specific overviews on SAA-related topics and comparison of SAA with other potential acute-phase reactants.

Thank you very much in advance for your consideration, and we sincerely hope to welcome you as a contributor to our Special Issue on SAA.

Prof. Dr. Ernst Malle
Prof. Dr. János G. Filep
Guest Editors

Manuscript Submission Information

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Keywords

  • Serum Amyloid A in (Non)Mammalian systems
  • phylogenetic overview of different SAA isoforms
  • expression of SAA1-4 on mRNA and protein level
  • comparison of SAA with other acute-phase reactants
  • role of SAA during normal development and inflammation
  • role of SAA in cancer and other malignancies
  • potential role of SAA as a suitable biomarker during disease progression

Published Papers (2 papers)

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16 pages, 2738 KiB  
Article
Deficiency of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality and Lung Injury in Mice
by Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Luke W. Meredith, Brittany Dong, Qian Wang, Ling Guo, Xiangan Li, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Marlene E. Starr, Christopher M. Waters and Preetha Shridas
Int. J. Mol. Sci. 2023, 24(24), 17501; https://doi.org/10.3390/ijms242417501 - 15 Dec 2023
Cited by 1 | Viewed by 1106
Abstract
Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased [...] Read more.
Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated with chemokine production, chemokine and cytokine-mediated signaling, neutrophil chemotaxis, and neutrophil migration in SAA-TKO compared to WT mice. Consistently, myeloperoxidase activity and neutrophil counts were significantly increased in the lungs of septic SAA-TKO mice compared to WT mice. The in vitro treatment of HL-60, neutrophil-like cells, with SAA or SAA bound to a high-density lipoprotein (SAA-HDL), significantly decreased cellular transmigration through laminin-coated membranes compared to untreated cells. Thus, SAA potentially prevents neutrophil transmigration into injured lungs, thus reducing exacerbated tissue injury and mortality. In conclusion, we demonstrate for the first time that endogenous SAA plays a protective role in sepsis, including ameliorating lung injury. Full article
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14 pages, 1296 KiB  
Review
Interactions of Serum Amyloid A Proteins with the Blood-Brain Barrier: Implications for Central Nervous System Disease
by Michelle A. Erickson and Anvitha P. Mahankali
Int. J. Mol. Sci. 2024, 25(12), 6607; https://doi.org/10.3390/ijms25126607 - 15 Jun 2024
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Abstract
Serum amyloid A (SAA) proteins are highly conserved lipoproteins that are notoriously involved in the acute phase response and systemic amyloidosis, but their biological functions are incompletely understood. Recent work has shown that SAA proteins can enter the brain by crossing the intact [...] Read more.
Serum amyloid A (SAA) proteins are highly conserved lipoproteins that are notoriously involved in the acute phase response and systemic amyloidosis, but their biological functions are incompletely understood. Recent work has shown that SAA proteins can enter the brain by crossing the intact blood–brain barrier (BBB), and that they can impair BBB functions. Once in the central nervous system (CNS), SAA proteins can have both protective and harmful effects, which have important implications for CNS disease. In this review of the thematic series on SAA, we discuss the existing literature that relates SAA to neuroinflammation and CNS disease, and the possible roles of the BBB in these relations. Full article
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