Affinage

SERPINA3

Alpha-1-antichymotrypsin · UniProt P01011

Length
423 aa
Mass
47.7 kDa
Annotated
2026-06-10
87 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPINA3 (alpha-1-antichymotrypsin) is a secreted serine protease inhibitor whose canonical activity is the inhibition of cathepsin G, and whose dysregulation across many tissue contexts links it to inflammation, cancer progression, and developmental programs (PMID:36828876, PMID:41653436). Its protease-inhibitory function is direct and physiologically consequential: SERPINA3 blocks cathepsin G-mediated cleavage of the anti-apoptotic protein 14-3-3ε, shielding liver cancer cells from neutrophil extracellular trap-induced apoptosis (PMID:41653436), and disease-associated variants in generalized pustular psoriasis either abolish secretion or weaken cathepsin G inhibition (PMID:36828876). SERPINA3 transcription is governed by a convergent set of inducible factors that bind its promoter—Nur77/NR4A1 at a defined NBRE (-182/-175), NR1D1, STAT3, NF-κB p65, and the methylation-sensitive activators SP1/MZF1/ZBTB7B—integrating nuclear-receptor, cytokine, and inflammatory inputs (PMID:18248459, PMID:31278347, PMID:28412351, PMID:22246292, PMID:41653436, PMID:39957271); ZBTB7B-driven expression is further set by KCTD17-mediated ubiquitin degradation of the activator (PMID:40744994). Beyond its secreted role, SERPINA3 functions intracellularly: under oxidative stress its oxidized form complexes with HNRNP-K to drive transcription of POT1, UHRF1 and HIST2H2BE (PMID:31121493), it binds the Glo1 promoter to expand outer radial glia and promote cortical folding (PMID:36414636), and it is required for chondrogenesis by maintaining SOX9 protein levels (PMID:39097037). As a context-dependent signaling modulator, SERPINA3 activates or suppresses NF-κB (in part via SPOP-mediated repression of p65), PI3K/AKT, MAPK/ERK, and Wnt/β-catenin pathways to control proliferation, migration, invasion, and apoptosis (PMID:24817931, PMID:34957248, PMID:37417362, PMID:39957271, PMID:37594700). It also acts as an extracellular chaperone of amyloid-β42, where wild-type protein accelerates fibrillization while disease-linked polymorphisms alter oligomer lifetimes and neuronal cytotoxicity (PMID:33662018, PMID:34077500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2008 High

    Established the first defined transcriptional control element of SERPINA3, answering how its expression is switched on by a nuclear receptor.

    Evidence EMSA, ChIP, luciferase reporter and Nur77 gain/loss-of-function in HEK293T and HepG2 cells

    PMID:18248459

    Open questions at the time
    • Does not connect Nur77-driven SERPINA3 to a downstream physiological output
    • Other promoter elements not yet mapped
  2. 2012 Medium

    Showed SERPINA3 promoter activity is allele- and methylation-dependent through SP1/MZF1/ZBTB7B, and linked its overexpression to reduced adhesion and apoptosis resistance.

    Evidence Luciferase reporter with methylated/unmethylated constructs, SNP allelic comparison, and overexpression with adhesion/apoptosis assays in JEG-3 trophoblasts

    PMID:22246292

    Open questions at the time
    • Functional readout limited to one trophoblast line
    • Mechanism linking adhesion/apoptosis phenotype to protease inhibition unresolved
  3. 2017 High

    Expanded the transcriptional network by placing STAT3 and a NR4A1/NR1D1 nuclear-receptor axis upstream of SERPINA3 in distinct tissues.

    Evidence ChIP/ChIP-qPCR, luciferase reporter, RNAi knockdown, and migration/invasion assays in melanoma and hepatocytes

    PMID:28412351 PMID:31278347

    Open questions at the time
    • Whether these factors act combinatorially on the same promoter is untested
    • Cell-type specificity of each input not reconciled
  4. 2019 Medium

    Revealed an unexpected intracellular, redox-gated role: oxidized SERPINA3 complexes with HNRNP-K to drive transcription of telomere and HCC-promoting genes.

    Evidence Co-IP, promoter activity and transcript assays with oxidation-status correlation in HCC tissue

    PMID:31121493

    Open questions at the time
    • Single Co-IP without reciprocal validation of the complex
    • Mechanism of nuclear entry of a secreted serpin unexplained
  5. 2021 Medium

    Defined SERPINA3 as an amyloid-β42 chaperone whose effect on oligomer lifetime and neurotoxicity is dictated by sequence polymorphism.

    Evidence Recombinant wild-type vs variant protein with TEM, thioflavin T, Western blot, and SH-SY5Y cell-death assays

    PMID:33662018 PMID:34077500

    Open questions at the time
    • In vitro reconstitution only; no in vivo amyloid pathology test
    • Structural basis of polymorphism-dependent chaperoning not determined
  6. 2022 High

    Demonstrated that glycosylation controls stress-induced SERPINA3 secretion and that it relocates to apical tubular membranes in kidney disease, linking post-translational modification to its trafficking.

    Evidence Site-directed mutagenesis of glycosylation sites, glycanase treatment, secretion and localization assays in vitro and rat AKI model (murine ortholog)

    PMID:35147994

    Open questions at the time
    • Functional consequence of membrane relocation untested
    • Conducted on murine ortholog
  7. 2022 Medium

    Uncovered a developmental nuclear function in which SERPINA3 binds the Glo1 promoter to expand outer radial glia and induce human-type cortical folding.

    Evidence In vivo overexpression in mouse brain, oRG/neuron quantification, ChIP for Glo1 promoter binding, and knock-in behavioral testing

    PMID:36414636

    Open questions at the time
    • How a secreted serpin engages a promoter is mechanistically unresolved
    • Glo1 as the sole effector not established
  8. 2023 High

    Provided the clearest enzymatic-to-phenotype chain: SERPINA3 inhibits cathepsin G cleavage of 14-3-3ε to protect cancer cells from NET-induced death, with NF-κB p65 driving its expression.

    Evidence siRNA/ASO knockdown, Western blot for 14-3-3ε cleavage, ChIP for p65 binding, and apoptosis assays in liver cancer

    PMID:41653436

    Open questions at the time
    • Whether this mechanism generalizes beyond liver cancer untested
    • Stoichiometry of SERPINA3-cathepsin G inhibition in this context not quantified
  9. 2023 Medium

    Established SERPINA3 as a bidirectional signaling modulator across vascular, lung, urological, and cardiac systems, activating or suppressing NF-κB, Wnt/β-catenin, and SPOP-dependent pathways depending on context.

    Evidence siRNA/overexpression with Western blot pathway readouts, DIA proteomics, and pharmacological epistasis (XAV-939) across multiple cell and animal models

    PMID:34957248 PMID:37417362 PMID:37594700 PMID:38006519

    Open questions at the time
    • Direction of NF-κB regulation is opposite across tissues without a unifying mechanism
    • Direct molecular targets of pathway modulation mostly inferred from phosphorylation states
  10. 2023 High

    Linked SERPINA3 loss-of-function variants to generalized pustular psoriasis through impaired secretion or weakened cathepsin G inhibition, tying its canonical enzymatic activity to human disease.

    Evidence NGS variant identification, secretion assay, and cathepsin G enzymatic inhibition assay with patient-derived mutants

    PMID:36828876

    Open questions at the time
    • Causality at the organismal/genetic-segregation level not detailed here
    • Downstream inflammatory consequence of failed cathepsin G inhibition not directly shown
  11. 2024 High

    Defined a non-redundant developmental requirement for SERPINA3 in chondrogenesis via maintenance of the master regulator SOX9.

    Evidence siRNA silencing during in vitro chondrogenesis with RNA-seq, histology, biochemical proteoglycan assay, and SOX9 Western blot, with osteogenesis as specificity control

    PMID:39097037

    Open questions at the time
    • Mechanism by which SERPINA3 stabilizes SOX9 protein unknown
    • Whether protease-inhibitory activity is required not tested
  12. 2025 High

    Connected SERPINA3 abundance to an upstream ubiquitin-degradation switch (KCTD17→Zbtb7b) and to anti-fibrotic action in MASH, providing a druggable axis.

    Evidence KCTD17 depletion, Zbtb7b ubiquitination assay, hepatic stellate cell Par2/TGFβ activation assays, and pharmacological Kctd17 inhibition in dietary MASH mice

    PMID:40744994

    Open questions at the time
    • Demonstrated in murine ortholog
    • Whether secreted SERPINA3 acts on stellate cells via protease inhibition not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SERPINA3 can act both as a secreted protease inhibitor/chaperone and as a promoter-binding nuclear regulator, and what mechanism dictates its opposite effects on NF-κB and proliferation across tissues.
  • No structural model reconciling secreted and nuclear functions
  • No unifying mechanism for context-dependent signaling direction
  • Whether nuclear/promoter-binding activities require the serpin reactive-center loop is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005576 extracellular region 3 GO:0005634 nucleus 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-5357801 Programmed Cell Death 2
Partners
CTSGHNRNPKNR1D1NR4A1RELASTAT3ZBTB7B

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Nur77 (nuclear receptor NR4A1) directly transactivates the SERPINA3 gene by binding to a Nur77 responsive element (NBRE) located at -182 to -175 in the SERPINA3 promoter, as demonstrated by electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), and luciferase reporter assays; Nur77 overexpression increased SERPINA3 expression while RNA interference-mediated knockdown of Nur77 decreased it. EMSA, ChIP, luciferase reporter assay, RNA interference knockdown and overexpression in HEK293T and HepG2 cells The FEBS journal High 18248459
2017 STAT3 directly drives SERPINA3 transcription in melanoma cells; STAT3 binds the SERPINA3 promoter (validated by ChIP-qPCR), and STAT3 knockdown reduces SERPINA3 expression and impairs melanoma cell migration and invasion. ChIP-qPCR, RNA interference (STAT3 knockdown), global and JAK/STAT-specific gene expression profiling, migration/invasion functional assays Laboratory investigation; a journal of technical methods and pathology High 31278347
2017 ApoA4 stimulates SERPINA3 gene expression in hepatocytes via the nuclear receptors NR4A1 and NR1D1, which bind the SERPINA3 promoter; this was verified by ChIP, luciferase reporter assay, and RNA interference-mediated knockdown of NR4A1 or NR1D1. ChIP, luciferase reporter assay, siRNA knockdown of NR4A1/NR1D1, in vivo and in vitro expression analysis Biochemical and biophysical research communications High 28412351
2019 SERPINA3 interacts with heterogeneous nuclear ribonucleoprotein K (HNRNP-K) under oxidative stress (H2O2 exposure); the SERPINA3-HNRNP-K complex enhances promoter activity and transcript levels of POT1, UHRF1, and HIST2H2BE. The amount of co-immunoprecipitated HNRNP-K correlates with the level of SERPINA3 oxidation; inhibition of SERPINA3 oxidation suppressed transcriptional activity of the complex. Co-immunoprecipitation (Co-IP), promoter activity assays, transcript quantification, correlative analysis of SERPINA3 oxidation status in HCC tissues Redox biology Medium 31121493
2012 The SERPINA3 promoter is transcriptionally activated by the transcription factors SP1, MZF1, and ZBTB7B; the level of activation is allele-dependent (rs1884082 SNP), with the T allele induced more strongly than the G allele; when the promoter was methylated, ZBTB7B response became allele-specific. Overexpression of SERPINA3 in JEG-3 trophoblast cells decreased cell adhesion to extracellular matrix and neighboring cells but protected cells from apoptosis. Luciferase reporter assay with methylated/unmethylated promoter constructs, transfection of transcription factors, SNP allelic comparison, SERPINA3 overexpression in JEG-3 cells with adhesion and apoptosis assays Human molecular genetics Medium 22246292
2023 SERPINA3 variants identified in generalized pustular psoriasis (GPP) impair cathepsin G inhibitory function: one deletion variant (c.1246_1247del) produces a mutant protein that is not secreted and thus cannot inhibit cathepsin G; two missense variants reduce the ability of ACT (SERPINA3 protein) to inhibit cathepsin G enzymatic activity in functional assays. Next-generation sequencing, bioinformatic analysis, secretion assay of mutant vs wild-type SERPINA3, cathepsin G enzymatic inhibition assay with mutant proteins Journal of human genetics High 36828876
2021 Polymorphic SERPINA3 (I308T variant, rs142398813, and SAMP8-type Serpina3) prolongs the oligomeric state of Aβ42 peptide compared to wild-type SERPINA3, resulting in sustained oligomeric forms (trimers, tetramers) and increased neuronal cell death in SH-SY5Y cells; wild-type SERPINA3 accelerates Aβ42 fibrillization as a molecular chaperone. Transmission electron microscopy (TEM), Western blot (oligomer detection), thioflavin T assay, SH-SY5Y neuroblastoma cell death assay, comparison of recombinant wild-type vs polymorphic SERPINA3 proteins PloS one Medium 33662018
2021 Polymorphic SERPINA3-R124C acts as a 'benign chaperone' that shortens the lifetime of small soluble Aβ42 oligomers and converts Aβ42 into high-molecular aggregates more rapidly than wild-type SERPINA3, resulting in less cytotoxicity to SH-SY5Y cells compared to Aβ42 preincubated with wild-type SERPINA3. Transmission electron microscopy, thioflavin T assay, Western blot, SH-SY5Y cell viability assay with recombinant wild-type vs R124C SERPINA3 Bioscience, biotechnology, and biochemistry Medium 34077500
2022 Serpina3c/k (murine ortholog) is glycosylated at multiple N-glycosylation sites; during cellular stress (H2O2 or starvation), serpina3c/k secretion is increased and the secreted protein exhibits higher molecular weight. Site-directed mutagenesis of all four glycosylation sites (quadruple mutant) abolishes stress-induced secretion increase. In chronic kidney disease, serpina3c/k relocates from the cytoplasm to the apical tubular membrane. FLAG-tagged transfection, glycanase treatment, site-directed mutagenesis of glycosylation sites, Western blot, immunofluorescence/fractionation in kidney cells, in vivo rat acute kidney injury model FASEB journal High 35147994
2018 SERPINA3 silencing in high-metastatic colon cancer cells (HT-29LMM, KM-12L4) reduced cell migration and invasion in vitro and decreased expression of MMP-2 and MMP-9; in vivo, SERPINA3 siRNA reduced liver metastasis in mice and down-regulated Mmp-2, Mmp-9, and PCNA in metastatic lesions. siRNA knockdown, wound-healing assay, Transwell invasion assay, ELISA for MMP-2/MMP-9, in vivo mouse liver metastasis model with immunohistochemistry Digestive diseases and sciences Medium 29855767
2013 SERPINA3 promotes endometrial cancer cell proliferation by regulating G2/M cell cycle checkpoint and inhibiting apoptosis; the pro-proliferative effect is associated with activation of MAPK/ERK1/2 and PI3K/AKT signaling pathways. SERPINA3 gain- and loss-of-function in endometrial cancer cell lines, cell cycle analysis, apoptosis assay, Western blot for ERK1/2 and AKT phosphorylation International journal of clinical and experimental pathology Medium 24817931
2022 SERPINA3 overexpression in human neocortical development promotes outer radial glia (oRG) proliferation and increases upper-layer neurons, inducing cortical folding; downstream target Glo1 is involved, with SERPINA3 binding to the Glo1 promoter. Knock-in mice overexpressing SERPINA3 showed enhanced cognitive abilities. Overexpression in mouse brain (in vivo), quantification of oRG cells and neuron numbers, ChIP to demonstrate SERPINA3 binding to Glo1 promoter, knock-in mouse behavioral testing Cell discovery Medium 36414636
2023 SERPINA3 knockdown in vascular smooth muscle cells (RASMCs) attenuates proliferation and migration, and inhibits phosphorylation of IκBα and its downstream NF-κB pathway; secreted SERPINA3 protein increases expression of inflammatory factors in HUVECs. siRNA knockdown in RASMCs, EdU proliferation assay, scratch migration assay, Western blot for phospho-IκBα/NF-κB, recombinant SERPINA3 protein stimulation of HUVECs with RT-PCR for inflammatory factors Frontiers in cardiovascular medicine Medium 34957248
2023 SERPINA3 overexpression in lung cancer cells inhibits NF-κB signaling by upregulating SPOP (speckle-type POZ protein), which in turn suppresses NF-κB p65; identified by data-independent acquisition mass spectrometry and validated by Western blot in cell lines and xenograft tumors. DIA mass spectrometry proteomics, SERPINA3 overexpression, Western blot validation of SPOP and NF-κB p65, xenograft mouse model International journal of oncology Medium 37417362
2023 SERPINA3 inhibits cathepsin G (CTSG)-mediated cleavage of the anti-apoptotic protein 14-3-3ε in liver cancer cells, thereby protecting cells from neutrophil extracellular trap (NET)-induced apoptosis; NF-κB (p65) directly binds the SERPINA3 promoter to govern its expression in liver cancer. siRNA knockdown of SERPINA3, Western blot for 14-3-3ε cleavage, ChIP for p65 binding to SERPINA3 promoter, cell viability/apoptosis assays, antisense oligonucleotide targeting of SERPINA3 Cell reports High 41653436
2024 SERPINA3 is required for chondrogenic differentiation: its expression is markedly induced at early time points during in vitro chondrogenesis; siRNA silencing of SERPINA3 reduces cartilage pellet size, proteoglycan content, and downregulates ECM formation genes; SERPINA3 silencing markedly reduces SOX9 protein levels at early time points, suggesting SERPINA3 regulates the master transcriptional regulator SOX9 of chondrogenesis. The effect is specific to chondrogenesis (not osteogenesis). siRNA knockdown during in vitro chondrogenesis, RNA sequencing, DMMB assay, safranin-O staining, Western blot for SOX9, comparison with osteogenesis Matrix biology : journal of the International Society for Matrix Biology High 39097037
2025 KCTD17 regulates SERPINA3 (murine Serpina3k) expression by facilitating ubiquitin-mediated degradation of Zbtb7b (a transcriptional activator of SERPINA3); KCTD17 depletion increases SERPINA3/Serpina3k levels. Increased SERPINA3 reduces liver fibrosis in MASH by inhibiting Par2/TGFβ-mediated activation of hepatic stellate cells. Pharmacological inhibition of Kctd17 reverses MASH-induced liver fibrosis in mice. KCTD17 depletion in mouse models, ubiquitin-mediated degradation assay for Zbtb7b, measurement of SERPINA3/Serpina3k secretion, hepatic stellate cell activation assays (Par2/TGFβ pathway), dietary rodent MASH models, pharmacological inhibition in vivo Experimental & molecular medicine High 40744994
2025 Nur77 (NR4A1) promotes SERPINA3 transcription by binding to the SERPINA3 promoter region (-182 to -175), upregulating SERPINA3 expression and activating the Wnt/β-catenin pathway; SERPINA3 knockdown alleviates cisplatin-induced HK-2 cell injury (increased viability/proliferation, decreased apoptosis and inflammation); the protective effect of Nur77 knockdown is antagonized by SERPINA3 overexpression. ChIP assay, dual-luciferase reporter assay, siRNA knockdown of Nur77 and SERPINA3, SERPINA3 overexpression rescue, flow cytometry for apoptosis, ELISA for cytokines Nephrology (Carlton, Vic.) Medium 39957271
2023 SERPINA3 overexpression activates Wnt/β-catenin signaling to protect bladder epithelial cells (HBlEpCs) from apoptosis and promote cell growth; inhibition of Wnt/β-catenin with XAV-939 abolished the protective effect of serpina3n overexpression against cyclophosphamide-induced cystitis. Serpina3n overexpression in mouse IC/BPS model and HBlEpC cells, CCK-8/flow cytometry assays, Western blot for β-catenin, pharmacological inhibition (XAV-939) as epistasis test International urology and nephrology Medium 37594700
2024 LAMB3 upregulates SERPINA3 expression to promote intestinal inflammation via the integrin α3β1/FAK pathway; RNA sequencing and replenishment experiments showed that SERPINA3 is a downstream effector of LAMB3 in IBD intestinal epithelial cells. RNA sequencing after LAMB3 knockdown, replenishment (rescue) experiment with SERPINA3 re-expression, RT-qPCR, Western blot, dual-luciferase and ChIP-qPCR for LAMB3 regulation by p65 Inflammatory bowel diseases Medium 37454278
2025 SERPINA3 promotes cell proliferation, wound healing, and activates ERK and AKT signaling pathways in human dermal fibroblasts; SERPINA3 expression is downregulated in aged fibroblasts and further reduced by oxidative stress. RNA-seq analysis of aged fibroblasts, SERPINA3 gain/loss-of-function, proliferation and wound-healing assays, Western blot for ERK and AKT phosphorylation BMB reports Low 40495483
2024 SERPINA3 downregulation contributes to aromatase inhibitor (AI) resistance in ER-positive breast cancer; ANKRD11 functions as a downstream effector of SERPINA3 and induces AI insensitivity by interacting with and activating HDAC3. HDAC3 inhibition reverses AI resistance associated with decreased SERPINA3 and increased ANKRD11. Dataset screening (5 datasets), SERPINA3 knockdown/overexpression in cell lines, Co-IP for ANKRD11-HDAC3 interaction, HDAC3 activity assay, HDAC3 inhibitor rescue Communications biology Medium 37414914
2024 SERPINA3 and LCN2 are upregulated in osteoblastic prostate cancer (BPCa) cells via osteoblast-derived extracellular vesicles in a co-culture system; enhanced expression of SERPINA3 and LCN2 promotes osteogenesis and suppresses BPCa cell proliferation in co-culture and mouse xenograft models. OB-BPCa co-culture system, extracellular vesicle-mediated transfer assay, xenograft mouse experiments with intracaudal injection, proliferation assays Molecular oncology Medium 37408474
2023 SerpinA3 promotes myocardial ischemia-reperfusion injury by activating NF-κB signaling: SerpinA3 knockdown inhibited p65 phosphorylation in myocardial tissues and reduced H2O2-induced inflammation, oxidative stress, and apoptosis in cardiomyocytes in vitro and improved cardiac function in vivo. siRNA knockdown of SerpinA3 in rat IR model and in vitro H2O2 model, Western blot for p65 phosphorylation, flow cytometry/TUNEL for apoptosis, cardiac function measurements Molecular biotechnology Low 38006519
2025 SERPINA3 overexpression in prostate cancer cells activates IL-17 and TNFα signaling pathways by promoting CXCL2 expression, thereby increasing M1 macrophage recruitment into the tumor microenvironment and inhibiting cancer cell proliferation and invasion. Colony formation assay, Transwell assay, subcutaneous xenograft in mice, pathway analysis by RNA-seq/Western blot, CXCL2 expression measurement Brazilian journal of medical and biological research Low 40367014
2023 CTSC (cathepsin C) induces SERPINA3 expression in glioma cells via STAT3 signaling: CTSC activates STAT3, which mediates upregulation of SERPINA3 expression, and the CTSC/STAT3/SERPINA3 axis promotes glioma cell migration, invasion, and EMT. Transwell assay, RT-qPCR, Western blot for STAT3 and SERPINA3, CTSC overexpression/knockdown in glioma cells Gene Low 37925117
2024 SERPINA3 is expressed by a SERPINA3+ reactive astrocyte subtype (Ast.5) specifically enriched in the vicinity of neuritic amyloid plaques in human neocortex, as identified by spatial transcriptomics and validated at the protein level by immunofluorescence co-registered with immunohistochemistry. Spatial transcriptomics with distance-based analytic strategy, immunohistochemistry, immunofluorescence protein-level validation bioRxivpreprint Low 39605680
2025 Brain-specific SERPINA3N (murine) overexpression does not alter neuronal or glial development under homeostasis; however, under pathological conditions, SERPINA3N overexpression drives a pro-inflammatory response to brain injury, exacerbates blood-brain barrier dysfunction, promotes neurodegeneration through apoptotic neuronal loss, and disrupts oligodendroglial differentiation and myelination following neonatal brain injury. Brain-specific genetic overexpression tools in mice, neonatal brain injury model, cellular markers for neurons/glia/oligodendrocytes, BBB permeability assays, apoptosis assays bioRxivpreprint Medium bio_10.1101_2025.09.09.675167

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 SERPINA3 (aka alpha-1-antichymotrypsin). Frontiers in bioscience : a journal and virtual library 123 17485262
2006 Expressional and epigenetic alterations of placental serine protease inhibitors: SERPINA3 is a potential marker of preeclampsia. Hypertension (Dallas, Tex. : 1979) 114 17088445
2005 Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization. The Journal of experimental medicine 87 15795238
2012 Genetic and epigenetic mechanisms collaborate to control SERPINA3 expression and its association with placental diseases. Human molecular genetics 86 22246292
2023 SERPINA3: Stimulator or Inhibitor of Pathological Changes. Biomedicines 66 36672665
2008 Elevated expression of SerpinA1 and SerpinA3 in HLA-positive cervical carcinoma. The Journal of pathology 51 18438953
2005 Alpha-1-antichymotrypsin (ACT or SERPINA3) polymorphism may affect age-at-onset and disease duration of Alzheimer's disease. Neurobiology of aging 50 16137793
1996 Polymorphism in AACT gene may lower age of onset of Alzheimer's disease. Neuroreport 50 8730823
2018 SERPINA3 Silencing Inhibits the Migration, Invasion, and Liver Metastasis of Colon Cancer Cells. Digestive diseases and sciences 48 29855767
2017 Up-regulation of SERPINA3 correlates with high mortality of melanoma patients and increased migration and invasion of cancer cells. Oncotarget 48 27213583
2017 Differential overexpression of SERPINA3 in human prion diseases. Scientific reports 44 29142239
2021 Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells. Breast cancer (Tokyo, Japan) 42 33569740
2014 SERPINA3 promotes endometrial cancer cells growth by regulating G2/M cell cycle checkpoint and apoptosis. International journal of clinical and experimental pathology 42 24817931
2021 CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS. Neurology(R) neuroimmunology & neuroinflammation 35 33436375
2019 SERPINA3 is a key modulator of HNRNP-K transcriptional activity against oxidative stress in HCC. Redox biology 34 31121493
2004 Expression patterns of murine antichymotrypsin-like genes reflect evolutionary divergence at the Serpina3 locus. Journal of molecular evolution 33 15638460
2019 Search for novel STAT3-dependent genes reveals SERPINA3 as a new STAT3 target that regulates invasion of human melanoma cells. Laboratory investigation; a journal of technical methods and pathology 31 31278347
2011 Expression of the serine protease inhibitor serpinA3 in human colorectal adenocarcinomas. Oncology letters 30 22866096
2017 Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in hepatocytes. Biochemical and biophysical research communications 28 28412351
2021 The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease. Frontiers in cardiovascular medicine 27 34957248
2024 Regulation of CNS pathology by Serpina3n/SERPINA3: The knowns and the puzzles. Neuropathology and applied neurobiology 25 38647003
2019 Discovery of SERPINA3 as a candidate urinary biomarker of lupus nephritis activity. Rheumatology (Oxford, England) 25 30285245
2022 Sinensetin attenuates IL-1β-induced cartilage damage and ameliorates osteoarthritis by regulating SERPINA3. Food & function 24 36056701
2017 SERPINA3 induced by astroglia/microglia co-culture facilitates glioblastoma stem-like cell invasion. Oncology letters 23 29399139
2021 CircSERPINA3 regulates SERPINA3-mediated apoptosis, autophagy and aerobic glycolysis of prostate cancer cells by competitively binding to MiR-653-5p and recruiting BUD13. Journal of translational medicine 22 34861864
2008 Alpha 1-antichymotrypsin/SerpinA3 is a novel target of orphan nuclear receptor Nur77. The FEBS journal 22 18248459
2019 Clinical significance and role of up-regulation of SERPINA3 expression in endometrial cancer. World journal of clinical cases 21 31423431
2005 Alpha1-antichymotrypsin gene (SERPINA3) A/T polymorphism as a risk factor for aneurysmal subarachnoid hemorrhage. Stroke 20 15718509
1990 A physical map of the human PI and AACT genes. Genomics 19 1973140
2010 Comparative analysis of the human urinary proteome by 1D SDS-PAGE and chip-HPLC-MS/MS identification of the AACT putative urinary biomarker. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 18 21093387
2022 Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury. Frontiers in immunology 17 36304455
2020 Exome sequencing identifies a recurrent variant in SERPINA3 associating with hereditary susceptibility to breast cancer. European journal of cancer (Oxford, England : 1990) 17 33279852
2023 SERPINA3: A novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke. CNS neuroscience & therapeutics 16 37721405
2022 Human SERPINA3 induces neocortical folding and improves cognitive ability in mice. Cell discovery 16 36414636
2023 Overexpression of SERPINA3 suppresses tumor progression by modulating SPOP/NF‑κB in lung cancer. International journal of oncology 15 37417362
2021 Polymorphic SERPINA3 prolongs oligomeric state of amyloid beta. PloS one 15 33662018
2024 LncRNA SNHG1 facilitates colorectal cancer cells metastasis by recruiting HNRNPD protein to stabilize SERPINA3 mRNA. Cancer letters 14 39233042
2006 The alanine/threonine polymorphism of the alpha-1-antichymotrypsin (SERPINA3) gene and ruptured intracranial aneurysms in the Japanese population. Cerebrovascular diseases (Basel, Switzerland) 14 16968986
2000 Association of serum AACT levels and AACT signal polymorphism with late-onset Alzheimer's disease in Northern Ireland. International journal of geriatric psychiatry 14 10713585
2022 Transient response of serpinA3 during cellular stress. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 35147994
2021 Increased SERPINA3 Level Is Associated with Ulcerative Colitis. Diagnostics (Basel, Switzerland) 12 34943607
2023 Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/β-catenin signal. International urology and nephrology 11 37594700
2009 Polymorphism rs4934 of SERPINA3 and sporadic intracranial aneurysms in the Chinese population. Cerebrovascular diseases (Basel, Switzerland) 11 19907165
2023 SERPINA3-ANKRD11-HDAC3 pathway induced aromatase inhibitor resistance in breast cancer can be reversed by HDAC3 inhibition. Communications biology 10 37414914
2024 LAMB3 Promotes Intestinal Inflammation Through SERPINA3 and Is Directly Transcriptionally Regulated by P65 in Inflammatory Bowel Disease. Inflammatory bowel diseases 9 37454278
2023 Newly revealed variants of SERPINA3 in generalized pustular psoriasis attenuate inhibition of ACT on cathepsin G. Journal of human genetics 9 36828876
2023 Circular SERPINA3 and its target microRNA-944 as potential biomarkers in hepatitis C virus-induced hepatocellular carcinoma in Egyptian population. Non-coding RNA research 9 37305177
2023 Osteoblast-derived extracellular vesicles exert osteoblastic and tumor-suppressive functions via SERPINA3 and LCN2 in prostate cancer. Molecular oncology 9 37408474
2021 The acute phase response protein SERPINA3 is increased in tear fluid from the unaffected eyes of patients with unilateral acute anterior uveitis. Journal of ophthalmic inflammation and infection 9 34212267
2006 SERPINA3 polymorphism is not associated with primary intracerebral hemorrhage in a Polish population. Stroke 8 16424370
2025 Exploring SERPINA3 as a neuroinflammatory modulator in Alzheimer's disease with sex and regional brain variations. Metabolic brain disease 7 39754632
2024 SERPINA3 is a marker of cartilage differentiation and is essential for the expression of extracellular matrix genes during early chondrogenesis. Matrix biology : journal of the International Society for Matrix Biology 7 39097037
2022 HOXA-AS2 enhances GBM cell malignancy by suppressing miR-2116-3p thereby upregulating SERPINA3. BMC cancer 7 35387643
2021 DNA methylation status of SERPINA3 gene involved in mRNA expression in three cattle breeds. Animal biotechnology 6 33847248
2002 A novel porcine gene, alpha-1-antichymotrypsin 2 (SERPINA3-2): sequence, genomic organization, polymorphism and mapping. Gene 6 12119105
2023 CTSC promoted the migration and invasion of glioma cells via activation of STAT3/SERPINA3 axis. Gene 5 37925117
2022 Neurorescuing effect of Cinacalcet against hypercalcemia-induced nerve injury in chronic kidney disease via TRAF2/cIAP1/KLF2/SERPINA3 signal axis. Cell biology and toxicology 5 35635602
2022 Cloning, Expression, and Functional Analysis of the Full-Length cDNA of Acetyl-CoA C-acetyltransferase (AACT) Genes Related to Terpenoid Synthesis in Platycodon grandiflorus. Protein and peptide letters 5 36045540
2024 Spatial Transcriptomic Analysis Identifies a SERPINA3-Expressing Astrocytic State Associated with the Human Neuritic Plaque Microenvironment. bioRxiv : the preprint server for biology 4 39605680
2019 Determination of genetic effects of SERPINA3 on important growth traits in beef cattle. Animal biotechnology 4 30929567
2024 Immunohistochemical Expression of the SERPINA3 Protein in Uterine Fibroids. Current pharmaceutical biotechnology 3 38204235
2024 α1-Antichymotrypsin Complex (SERPINA3) Is an Independent Predictor of All-Cause but Not Cardiovascular Mortality in Patients Hospitalized for Chest Pain of Suspected Coronary Origin. Cardiology 3 38402860
2023 SerpinA3 Promotes Myocardial Infarction in Rat and Cell-based Models. Molecular biotechnology 3 38006519
2022 Association between copy number variation of SERPINA3-1 gene and growth traits in Chinese cattle. Animal biotechnology 3 35209806
2025 SERPINA3 predicts long-term neurological outcomes and mortality in patients with intracerebral hemorrhage. Cell death & disease 2 40157917
2025 Overexpression of SERPINA3 inhibits castration-resistant prostate cancer progression by enhancing M1 macrophage recruitment via CXCL2 upregulation. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 2 40367014
2024 SMOC2, OGN, FCN3, and SERPINA3 could be biomarkers for the evaluation of acute decompensated heart failure caused by venous congestion. Frontiers in cardiovascular medicine 2 39717447
2023 Hypothermic machine perfusion reduces donation after circulatory death liver ischemia-reperfusion injury through the SERPINA3-mediated PI3Kδ/Akt pathway. Human cell 2 38133876
2022 Serpin-A3 is Associated with Persistent Albuminuria in Adolescents with Secondary Podocytopathy, in a Region with High Prevalence of Chronic Kidney Disease of Unknown Origin. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 2 37205833
2025 Role of SerpinA3 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts. Investigative ophthalmology & visual science 1 40202736
2025 Maternal and Fetal SERPINA3 Polymorphisms and Risk of Preeclampsia: A Dyad and Triad Based Case-Control Study. Current issues in molecular biology 1 41296456
2024 PARD6A promotes lung adenocarcinoma cell proliferation and invasion through Serpina3. Cancer gene therapy 1 39300216
2021 Polymorphic SERPINA3-R124C reduces pathogenesis of its wild type by shortening the lifetime of oligomeric Aβ. Bioscience, biotechnology, and biochemistry 1 34077500
2026 SERPINA3 Promotes Glioblastoma Progression by Promoting APOE Expression and Regulating the PI3K/AKT/FOXO1 Pathway. Neurology India 0 41510858
2026 SERPINA3 facilitates malignant progression and remodels tumor immune microenvironment in glioma. Biochemistry and biophysics reports 0 41550507
2026 SERPINA3 mediates liver cancer cells escape from chemotherapy-induced neutrophil extracellular trap killing. Cell reports 0 41653436
2026 ELISA-based validation of differentially expressed Fibrinogen, S100A9, SERPINA3 and SERPINA6 proteins in Polycystic Ovary Syndrome (PCOS). Steroids 0 42034305
2026 Plasma SERPINA3 and its clinical correlates in adolescent major depressive disorder: an exploratory case-control study. BMC psychiatry 0 42163223
2026 Tamoxifen-pretreated MSC exosomes promote endocrine resistance in ER-positive breast cancer cells through the miR-137/Serpina3 axis: a mechanistic study. Breast cancer research : BCR 0 42169152
2025 Nur77 Promotes Inflammation in Cisplatin-Induced Acute Kidney Injury Through Transactivation of SERPINA3 Mediating Wnt/β-Catenin Pathway. Nephrology (Carlton, Vic.) 0 39957271
2025 SERPINA3: A Novel Therapeutic Target for Diabetes-Related Cognitive Impairment Identified Through Integrated Machine Learning and Molecular Docking Analysis. International journal of molecular sciences 0 40076571
2025 SERPINA3 in Diabetic Retinopathy: A Pilot Study Assessing the Impact of Prior COVID-19 Infection on Patients. Current eye research 0 40375599
2025 SERPINA3 is expressed in human adipocytes and modulated by TNF-α and vitamin B6. In vitro cellular & developmental biology. Animal 0 40425899
2025 SERPINA3 as a modulator of skin cell functionality in human dermal fibroblasts. BMB reports 0 40495483
2025 Hepatocyte KCTD17-mediated SERPINA3 inhibition determines liver fibrosis in metabolic dysfunction-associated steatohepatitis. Experimental & molecular medicine 0 40744994
2024 Decoding early-onset of colorectal cancer: Insights into SERPINA3 expression patterns. Heliyon 0 39584126
2001 [Analysis of the polymorphisms of the AACT, ERAB and NACP genes in 15 patients with Alzheimer's disease]. Zhonghua yi xue za zhi 0 11798857

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