SERPINB2 Human
Description
Biological Functions
Key roles of SERPINB2 include:
Role in Macrophage Biology
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SerpinB2 is constitutively expressed in large peritoneal macrophages (LPM) and inhibits migration by counteracting plasmin activity .
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RNA-Seq analysis revealed SerpinB2 suppresses Gata6-regulated genes involved in extracellular matrix interactions .
Stem Cell Toxicity and Differentiation
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SERPINB2 overexpression in stem cells reduces proliferation (5.08–10.13% apoptosis rate), migration (via MMP-2 suppression), and differentiation potential .
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Conversely, SERPINB2 knockdown enhances osteoblast/adipocyte differentiation and migration .
Clinical and Diagnostic Relevance
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Elevated SERPINB2 correlates with toxicity in human stem cells exposed to dioxins, UV irradiation, and chemotherapeutics .
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Integrated into oral-on-a-chip systems for rapid toxicity screening via GFP-tagged detection .
Production and Applications
Recombinant SERPINB2 (e.g., His-tagged 49 kDa protein produced in E. coli) is used for studying protease inhibition and immune modulation . Its roles in cancer (e.g., promoting tumor survival) and neurodegenerative diseases (e.g., inhibiting β-amyloid fibril formation) are under investigation .
Product Specs
SERPINB2, primarily found in keratinocytes, stimulated monocytes, and placental trophoblasts, is an inhibitory serpin. It exists mainly as a 47 kDa intracellular protein that is not glycosylated. Upon induction, it is secreted as a 60 kDa glycoprotein. Both forms effectively inhibit uPA, the only confirmed physiological target of SERPINB2.
To reconstitute the lyophilized SERPINB2, it is recommended to dissolve it in sterile 18MΩ-cm H2O at a concentration not less than 100µg/ml. This solution can be further diluted in other aqueous solutions.
(a) Analysis by RP-HPLC.
(b) Analysis by SDS-PAGE.
Serpin Peptidase Inhibitor Clade B (Ovalbumin) Member 2, Serine (Or Cysteine) Proteinase Inhibitor Clade B (Ovalbumin) Member 2, Placental Plasminogen Activator Inhibitor, Plasminogen Activator Inhibitor Type II (Arginine-Serpin), PAI2, PLANH2, Monocyte Arg-Serpin, Serpin B2, HsT1201, PAI.
Q&A
What is SERPINB2 and what cellular processes does it regulate?
SERPINB2 (Serpin Family B Member 2) is a member of the serine protease inhibitor family that functions as a plasminogen activator inhibitor (PAI-2) . It is one of the most highly inducible genes in monocytes and can constitute up to 1% of total cellular protein during inflammatory responses . Recent functional analyses have revealed that a key role of SERPINB2 is modulating proteotoxic stress . Additionally, it regulates cell proliferation, differentiation, and plays important roles in innate immunity and macrophage survival .
The protein structure follows the conserved SERPIN pattern with a globular domain containing critical central beta sheets and a reactive center loop (RCL) that protrudes from the main SERPIN body . This structure is essential for its protease inhibition mechanism and subsequent biological functions.
In which cell types and tissues is SERPINB2 expressed?
SERPINB2 exhibits tissue-specific and condition-dependent expression patterns:
This expression profile suggests SERPINB2 plays multiple tissue-specific roles, with particularly important functions in immune cells during inflammatory responses .
How is SERPINB2 expression experimentally measured in research settings?
For comprehensive evaluation of SERPINB2 expression, researchers employ multiple complementary techniques:
To map LPS-regulated SERPINB2 promoter regions, researchers have successfully used reporter constructs driven by the ~5 kb 5'-flanking region of the murine SERPINB2 gene with several deletion mutants transfected into murine macrophages .
How is SERPINB2 dysregulated in inflammatory diseases?
SERPINB2 shows significant dysregulation in multiple inflammatory conditions:
ChIP-seq data on SLE patients demonstrated higher H3K4me3 (a histone modification associated with active transcription) both downstream and upstream of the SERPINB2 transcription start site, corresponding with higher SERPINB2 mRNA levels in these patients . This epigenetic signature suggests chromatin remodeling contributes to SERPINB2 dysregulation in inflammatory diseases.
What is SERPINB2's role in stem cell toxicity and how can this be experimentally assessed?
SERPINB2 serves as a novel indicator of stem cell toxicity, with expression significantly increased in response to various toxic agents both in vitro and in vivo . When SERPINB2 expression is enhanced in stem cells, these functional effects are observed:
Researchers have noted that different toxic substances elicit varying degrees of SERPINB2 induction:
These observations suggest SERPINB2 could serve as a sensitive biomarker for toxicity screening, particularly for human stem cell-based in vitro toxicity assessment platforms .
How does SERPINB2 expression correlate with cancer progression?
SERPINB2 expression has been associated with tumor promotion and poor prognosis in multiple cancer types:
Understanding the dual role of SERPINB2 in both suppressing cell growth and being associated with poor prognosis in certain cancers represents an important research paradox requiring further investigation into context-dependent functions .
What transcription factors and upstream signals regulate SERPINB2 expression?
Multiple transcription factors and signaling pathways regulate SERPINB2 expression:
Experimental evidence from C/EBP-β-null mouse embryonic fibroblasts (MEFs) and primary C/EBP-β-deficient peritoneal macrophages shows severely abrogated SERPINB2 expression in both constitutive and LPS-induced conditions, demonstrating the critical importance of C/EBP-β in SERPINB2 regulation .
What are the key promoter elements controlling SERPINB2 expression?
Mutation analyses have identified several critical regulatory elements in the SERPINB2 promoter:
These elements work in concert to achieve the high inducibility of SERPINB2 in response to inflammatory stimuli, particularly LPS . Researchers mapped these elements by transfecting reporter constructs driven by the ~5 kb 5'-flanking region of the murine SERPINB2 gene and several deletion mutants into murine macrophages .
What epigenetic mechanisms control SERPINB2 expression?
Epigenetic regulation plays a critical role in SERPINB2 expression, particularly in disease states:
Investigation of epigenetic regulation is critical given the aberrant expression of SERPINB2 in many human disease states and its highly dynamic expression patterns . ChIP-seq data has revealed higher H3K4me3 both downstream and upstream of the transcription start site in SLE patients, corresponding with increased mRNA levels .
What cellular and animal models are optimal for studying SERPINB2 functions?
Various models have been used to study different aspects of SERPINB2 regulation and function:
When selecting models, researchers should consider the specific aspect of SERPINB2 biology being investigated. For inflammatory regulation, macrophage models are preferable, while toxicity studies benefit from stem cell models .
How can protein-protein interactions between SERPINB2 and target proteases be studied?
Understanding SERPINB2's interactions with proteases requires specialized techniques:
Protein-protein docking screens based on structure have proven valuable for identifying novel SERPIN-protease pairs, specifically by predicting the fit of the SERPIN reactive center loop (RCL) into the protease active site .
What approaches best reveal SERPINB2's role in inflammatory responses?
To investigate SERPINB2's role in inflammation, researchers employ multiple complementary approaches:
For example, researchers have demonstrated that LPS induces the formation of C/EBP-β containing complexes with the SERPINB2 promoter using electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays , providing mechanistic insight into inflammatory regulation.
How might SERPINB2 be exploited as a biomarker for toxicity prediction?
SERPINB2 shows promise as a biomarker for toxicity prediction in stem cell-based platforms:
Researchers found that SERPINB2 expression is significantly increased in response to multiple "danger" signals, including bacterial lipopolysaccharide, hypoxia, and cytotoxic agents . By combining SERPINB2 expression analysis with stem cell models, researchers can develop sensitive screening platforms that provide valuable information on toxic compounds not normally detected by other somatic cell-based systems .
What unexplored antiviral functions might SERPINB2 possess?
SERPINB2's potential antiviral functions represent an emerging research area:
Analysis of bronchoalveolar lavage fluids (BALF) from COVID-19 patients revealed that SERPINB2 is one of several SERPINs upregulated in epithelial cells during infection . Correlation analysis showed that SERPINB2 expression levels correlate with those of canonical TNF-alpha and interferon-stimulated genes, suggesting participation in viral-induced inflammation responses .
How do contradictory findings regarding SERPINB2 in cell growth regulation reconcile in different contexts?
SERPINB2 exhibits context-dependent effects that require nuanced investigation:
The contrasting effects of SERPINB2 overexpression versus dioxin-induced expression highlight an important research consideration: SERPINB2 overexpression significantly induces apoptosis in human stem cells, but dioxin treatment, while increasing SERPINB2, does not induce apoptosis . This discrepancy likely results from differences in SERPINB2 expression levels and accompanying cellular context changes . Resolving such contradictions requires careful experimental design accounting for expression levels, cellular context, and interaction partners.
What aspects of SERPINB2 regulation remain poorly understood?
Despite significant progress, several aspects of SERPINB2 regulation remain unexplored:
The epigenetic control of SERPINB2 expression has not been previously extensively investigated despite its aberrant expression in many human disease states and highly dynamic expression patterns . This represents a significant knowledge gap that could be addressed through comprehensive epigenetic profiling.
What methodological limitations constrain current SERPINB2 research?
Current research faces several methodological challenges:
The cellular heterogeneity challenge is particularly evident in studies of SERPINB2 in complex tissues. Single-cell RNA-seq of bronchoalveolar lavage fluids from COVID-19 patients has begun to address this by allowing investigation of mRNA expression levels of individual SERPINs in different cell types at the site of infection .
How might emerging technologies advance SERPINB2 research?
Emerging technologies offer new opportunities for SERPINB2 investigation:
For instance, protein-protein docking screens enabled by improved computational methods have already identified novel SERPIN-protease pairs based on structure . These approaches are particularly valuable for understanding SERPINB2's potential role in antiviral responses by predicting interaction with proteases involved in viral replication cycles.
Product Science Overview
The SERPINB2 gene is located on chromosome 18 in humans and encodes a protein that is primarily found as a 47 kDa non-glycosylated intracellular protein. Upon induction, it can be secreted as a 60 kDa glycoprotein . The glycosylated and non-glycosylated forms of SERPINB2 are similarly effective as inhibitors of urokinase-type plasminogen activator (uPA), which is the only proven physiological target of SERPINB2 .
SERPINB2 functions as an inhibitor of uPA, a serine protease involved in the degradation of the extracellular matrix and the activation of other proteases. By inhibiting uPA, SERPINB2 plays a crucial role in regulating processes such as tissue remodeling, cell migration, and inflammation . The inhibition mechanism involves the formation of a stable complex between SERPINB2 and uPA, which prevents uPA from interacting with its substrates .
SERPINB2 is involved in various physiological and pathological processes. It is expressed in a variety of tissues, including the placenta, monocytes, and macrophages. Its expression is upregulated in response to inflammatory stimuli, indicating its role in the immune response . Additionally, SERPINB2 has been implicated in several diseases, including gingivitis and pre-eclampsia .
Due to its role in inhibiting uPA, SERPINB2 is of interest in cancer research, particularly in the context of tumor invasion and metastasis. By modulating the activity of uPA, SERPINB2 can potentially influence the invasive properties of cancer cells . Furthermore, its involvement in inflammatory responses makes it a target for studying inflammatory diseases and developing anti-inflammatory therapies .
