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Review
. 2023 Jan 7;11(1):156.
doi: 10.3390/biomedicines11010156.

SERPINA3: Stimulator or Inhibitor of Pathological Changes

Mateusz de Mezer  1 , Jan Rogaliński  1 , Stanisław Przewoźny  1 , Michał Chojnicki  1 , Leszek Niepolski  2 , Magdalena Sobieska  3 , Agnieszka Przystańska  4
Affiliations
Review

SERPINA3: Stimulator or Inhibitor of Pathological Changes

Mateusz de Mezer et al. Biomedicines. .

Abstract

SERPINA3, also called α-1-antichymotrypsin (AACT, ACT), is one of the inhibitors of serine proteases, one of which is cathepsin G. As an acute-phase protein secreted into the plasma by liver cells, it plays an important role in the anti-inflammatory response and antiviral response. Elevated levels of SERPINA3 have been observed in heart failure and neurological diseases such as Alzheimer's disease or Creutzfeldt-Jakob disease. Many studies have shown increased expression levels of the SERPINA3 gene in various types of cancer, such as glioblastoma, colorectal cancer, endometrial cancer, breast cancer, or melanoma. In this case, the SERPINA3 protein is associated with an antiapoptotic function implemented by adjusting the PI3K/AKT or MAPK/ERK 1/2 signal pathways. However, the functions of the SERPINA3 protein are still only partially understood, mainly in the context of cancerogenesis, so it seems necessary to summarize the available information and describe its mechanism of action. In particular, we sought to amass the existing body of research focusing on the description of the underlying mechanisms of various diseases not related to cancer. Our goal was to present an overview of the correct function of SERPINA3 as part of the defense system, which unfortunately easily becomes the "Fifth Column" and begins to support processes of destruction.

Keywords: DNA binding; MAPK/ERK 1/2; PI3K/AKT; SERPINA3; anti-inflammatory; antiapoptotic; α-1-antichymotrypsin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
SERPINA3 (serine protease inhibitor A3) gene: (A) chromosomal localization and canonical mRNA forms based on NCBI Genome data (https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=12, accessed on 21 December 2022); (B) scheme of canonical SERPINA3 protein; (C) protein products of alternative splicing: ACT-N (upper image) and ACT-T (lower image).
Figure 2
Figure 2
Tissue expression of the SERPINA3 gene (https://www.proteinatlas.org/ENSG00000196136-SERPINA3/tissue; accessed on 17 December 2022).
Figure 3
Figure 3
A decrease in SERPINA3 mRNA expression as a result of the inhibition of miR-137 by LncRNA GAS5 may cause lower apoptosis and/or fibrosis.
Figure 4
Figure 4
Possible role of SERPINA3 protein in cellular and extracellular processes.
See this image and copyright information in PMC

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