Affinage

SERPINA12

Serpin A12 · UniProt Q8IW75

Length
414 aa
Mass
47.2 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPINA12 (vaspin) is an adipokine of the serpin superfamily that functions both as a specific protease inhibitor and as a receptor-engaging signaling ligand, coordinating glucose metabolism, epithelial differentiation, vascular protection, and tissue homeostasis (PMID:23370777, PMID:22837305, PMID:18321232). Its defining biochemical activity is high-specificity inhibition of kallikrein 7 (KLK7/hK7) by the classical serpin mechanism, established by crystal structure, in vitro reconstitution with active-site mutagenesis, and detection of vaspin-hK7 complexes in human plasma; this protective inhibition shields insulin from hK7-mediated A/B-chain cleavage and improves glucose tolerance in vivo in a manner strictly dependent on serpin activity (PMID:23370777). The same protease-inhibitory function operates in skin, where loss-of-function nonsense variants in SERPINA12 cause autosomal recessive palmoplantar keratoderma: reduced KLK7 inhibition lowers the KLK7 substrates desmoglein-1 and corneodesmosin and drives epidermal acanthosis and hyperkeratosis (PMID:32247861). Independently of its serpin activity, vaspin signals through a cell-surface receptor complex of GRP78 and MTJ-1 (DnaJC1) recruited to the plasma membrane, activating Akt and AMPK; antibody blockade of GRP78 abolishes this signaling (PMID:22837305). Through GRP78 engagement and downstream PI3K/AKT, AMPK, ERK, STAT3, and PKA cascades, vaspin promotes insulin-independent GLUT4 translocation and muscle glucose uptake (PMID:30721136), suppresses NF-κB-driven inflammatory and adhesion programs in endothelium and adipocytes (PMID:24517399, PMID:28756250), enhances endothelial NO bioavailability and protects vascular cells from apoptosis (PMID:21893030, PMID:23284999), drives osteoblast differentiation and survival (PMID:23135225, PMID:31993071), and supports ovarian and luteal steroidogenesis, proliferation, and survival (PMID:32149334, PMID:33608490, PMID:31752432, PMID:33108345). In liver, GRP78-dependent AMPK activation reduces hepatocyte steatosis (PMID:35001345), and a TCF7L2/β-catenin-driven SERPINA12-GRP78-AKT/GSK3β feed-forward loop sustains hepatocellular carcinoma stemness and therapy resistance (PMID:36630996). Vaspin is also internalized into renal proximal tubular cells in a complex with HSPA1L and GRP78 via clathrin-mediated endocytosis, maintaining lysosomal and autophagic homeostasis (PMID:33742129).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2009 Low

    Establishing that an adipose-derived factor could improve metabolic phenotype defined vaspin as a candidate insulin-sensitizing adipokine and motivated mechanistic dissection.

    Evidence cDNA subtraction cloning from OLETF rat visceral WAT and recombinant protein administration to obese mice

    PMID:18321232

    Open questions at the time
    • No molecular receptor or pathway identified
    • Single lab foundational report without mechanistic resolution
  2. 2012 High

    Identifying the cell-surface GRP78/MTJ-1 complex answered how a secreted serpin transmits an intracellular signal, defining vaspin's receptor-based signaling arm.

    Evidence Tandem affinity purification, cell-surface biotin labeling, reciprocal co-IP in liver and hepatoma cells, and GRP78 antibody blockade of Akt/AMPK activation

    PMID:22837305

    Open questions at the time
    • Stoichiometry and structural basis of vaspin-GRP78 binding unresolved
    • Whether GRP78 transduces signal directly or via co-receptors not established
  3. 2013 High

    Solving the crystal structure and reconstituting KLK7 inhibition defined vaspin's primary enzymatic target and showed its metabolic effect operates by protecting insulin from proteolytic degradation rather than altering insulin sensitivity.

    Evidence Crystal structure, in vitro protease inhibition with active-site mutants, plasma co-IP of vaspin-hK7 complexes, euglycemic-hyperinsulinemic clamp, and isolated islet assays

    PMID:23370777

    Open questions at the time
    • Full repertoire of physiological vaspin protease targets beyond hK7 not mapped
    • Relationship between serpin activity and GRP78 signaling arm not reconciled
  4. 2016 Medium

    Linking vaspin to keratinocyte differentiation extended its serpin/KLK7 axis to epithelial biology and connected its loss to inflammatory skin pathology.

    Evidence Immunohistochemistry, siRNA knockdown in keratinocytes, immune cell co-culture, and a psoriasis-like mouse model

    PMID:26783881

    Open questions at the time
    • Whether skin effects are KLK7-dependent not directly tested in this work
  5. 2020 High

    Human loss-of-function genetics established SERPINA12 as a Mendelian disease gene and confirmed in vivo that its physiological role is KLK7 inhibition controlling epidermal differentiation.

    Evidence Whole-exome sequencing of patients, 3D skin equivalent knockdown, KLK7 activity assays, and quantification of KLK7 substrates desmoglein-1 and corneodesmosin

    PMID:32247861

    Open questions at the time
    • Genotype-phenotype variability and extracutaneous consequences of human deficiency not detailed
  6. 2021 High

    Defining vaspin internalization via an HSPA1L/GRP78/clathrin complex positioned receptor-mediated endocytosis upstream of organellar homeostasis in renal tubular cells.

    Evidence Co-IP of vaspin-HSPA1L-GRP78-clathrin complexes, vaspin-/- knockout mouse histology, and HSPA1L overexpression rescue

    PMID:33742129

    Open questions at the time
    • Whether endocytosis terminates or propagates GRP78 signaling unclear
    • Generality of this trafficking route to other tissues unknown
  7. 2023 High

    Showing a TCF7L2/β-catenin-driven SERPINA12-GRP78-AKT feed-forward loop in HCC reframed vaspin as a context-dependent tumor-promoting factor rather than a purely protective adipokine.

    Evidence Transcriptome profiling, TCF7L2 promoter-binding assay, SERPINA12-GRP78 co-IP, shRNA loss-of-function, and in vivo AAV knockdown sensitizing tumors to sorafenib

    PMID:36630996

    Open questions at the time
    • Reconciliation with hepatoprotective roles of vaspin in steatosis not addressed
    • Whether serpin activity contributes to the oncogenic loop untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How vaspin's serpin protease-inhibitory activity and its GRP78-receptor signaling arm are integrated—and which physiological outputs depend on which mode—remains unresolved.
  • No single study dissects serpin-dependent versus GRP78-dependent outputs in the same system
  • The protease degrading the anti-orexigenic factor inferred from CNS studies is unidentified
  • Structural basis and exact binding site for the vaspin-GRP78 interaction undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 2
Partners
CLTCDNAJC1HSPA1LHSPA90B1/GRP78KLK7
Complex memberships
vaspin-GRP78-MTJ-1 plasma membrane receptor complexvaspin-HSPA1L-GRP78 endocytic complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 Vaspin inhibits human kallikrein 7 (hK7) by classical serpin mechanism with high specificity in vitro. The crystal structure of vaspin was solved, vaspin-hK7 complexes were detected in human plasma, and co-expression was found in murine pancreatic β-cells. hK7 was shown to cleave human insulin in the A- and B-chain. Improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin was fully dependent on vaspin serpin activity (inactive mutants had no effect), and was not related to changes in insulin sensitivity by euglycemic-hyperinsulinemic clamp. Vaspin treatment of isolated pancreatic islets increased insulin concentration in media upon glucose stimulation without influencing insulin secretion, suggesting vaspin may inhibit insulin degradation by hK7 in circulation. Crystal structure determination; in vitro protease inhibition assay; active-site mutagenesis (inactive mutants); co-immunoprecipitation of vaspin-hK7 complexes from plasma; euglycemic-hyperinsulinemic clamp; isolated islet assay Cellular and molecular life sciences : CMLS High 23370777
2020 Loss-of-function homozygous nonsense variants in SERPINA12 cause autosomal recessive palmoplantar keratoderma. Reduced SERPINA12 expression in patients' skin biopsies and SERPINA12 knockdown in 3D skin equivalents produced epidermal acanthosis and hyperkeratosis. Mechanistically, decreased SERPINA12 expression led to reduced inhibition of kallikrein 7 (KLK7) activity, resulting in decreased levels of desmoglein-1 and corneodesmosin—two known KLK7 substrates required for normal epidermal differentiation. Whole-exome sequencing; 3D skin equivalent knockdown model; immunohistochemistry; KLK7 activity assay; protein quantification of KLK7 substrates (desmoglein-1, corneodesmosin) The Journal of investigative dermatology High 32247861
2012 Vaspin binds to cell-surface GRP78 (78-kDa glucose-regulated protein), which is recruited from ER to the plasma membrane under ER stress. Vaspin forms a complex with GRP78 and MTJ-1 (DnaJ homolog subfamily C member 1) on the plasma membrane, confirmed by tandem affinity purification, cell-surface biotin labeling, and co-immunoprecipitation in liver tissues and H-4-II-E-C3 cells. Addition of recombinant vaspin increased phosphorylation of Akt and AMPK in a dose-dependent manner; anti-GRP78 antibodies completely abrogated vaspin-induced pAkt and pAMPK upregulation. Tandem affinity tag purification (HepG2 cells); cell-surface biotin labeling; co-immunoprecipitation; western blotting; antibody blockade of GRP78 Diabetes High 22837305
2023 In HCC, SERPINA12 expression is driven by TCF7L2 (a β-catenin effector) binding to the SERPINA12 promoter. Endogenous SERPINA12 promotes HCC stem cell self-renewal, therapy resistance, and metastasis by binding to GRP78, resulting in hyperactivation of the AKT/GSK3β/β-catenin signaling cascade forming a positive feed-forward loop. rAAV8-shSERPINA12 in vivo sensitized HCC cells to sorafenib. Transcriptome profiling; promoter binding assay (TCF7L2 to SERPINA12 promoter); co-immunoprecipitation (SERPINA12-GRP78 binding); loss-of-function (shRNA knockdown) with functional readouts; in vivo AAV-mediated knockdown Hepatology (Baltimore, Md.) High 36630996
2021 During internalization into proximal tubular cells (PTCs), vaspin forms a complex with HSPA1L (heat shock protein family A member 1-like) and GRP78. Both vaspin partners bind to clathrin heavy chain and are involved in endocytosis. Vaspin-/- obese mice showed enlarged and leaky lysosomes in PTCs with increased apoptosis. Overexpression of HSPA1L dissolved organelle stresses including autophagy impairment, placing vaspin/HSPA1L-mediated endocytosis upstream of organellar homeostasis in PTCs. Co-immunoprecipitation (vaspin-HSPA1L-GRP78 complex, clathrin interaction); vaspin-/- knockout mouse model with histological analysis; HSPA1L overexpression rescue experiment Communications biology High 33742129
2011 Vaspin is expressed in the hypothalamus and detected in cerebrospinal fluid of healthy individuals. Both peripheral (intraperitoneal) and central (intracerebroventricular) vaspin administration decreased food intake in obese db/db and lean C57BL/6 mice. In db/db mice, central vaspin treatment produced sustained blood glucose-lowering effects for at least 6 days after injection, suggesting vaspin inhibits a protease that degrades an anti-orexigenic factor. Western blotting (hypothalamus protein); ELISA (CSF vaspin); intracerebroventricular injection; intraperitoneal injection; food intake and blood glucose measurement in db/db and C57BL/6 mice Diabetologia Medium 21465327
2011 Vaspin protects vascular endothelial cells from free fatty acid (linoleic acid)-induced apoptosis through upregulation of the PI3K/Akt signaling pathway. Vaspin significantly increased Akt phosphorylation, prevented linoleic acid-induced impairment of Akt phosphorylation in insulin-stimulated endothelial cells, and the anti-apoptotic effect was abolished by the PI3K inhibitor Wortmannin. Cell culture (endothelial cells); western blotting for Akt phosphorylation; PI3K inhibitor (Wortmannin) blockade; apoptosis assay Biochemical and biophysical research communications Medium 21893030
2012 Vaspin increases nitric oxide (NO) bioavailability in vascular endothelial cells by activating the STAT3 signaling pathway, stimulating eNOS phosphorylation (Ser1177) via STAT3, and increasing DDAH II (dimethylarginine dimethylaminohydrolase II) expression through STAT3-mediated stimulation of the DDAH II promoter, leading to reduced ADMA levels. Vaspin-induced NO increase was confirmed in isolated rat aorta. NO secretion assay (endothelial cells and isolated aorta); western blotting (STAT3, eNOS phosphorylation, DDAH II); DDAH II promoter-luciferase assay; vasorelaxation assay (isolated aorta) PloS one Medium 23284999
2014 Vaspin inhibits cytokine-induced NF-κB activation and expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin, MCP-1) in human aortic endothelial cells by activating AMPK. Vaspin increased phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. These effects were abolished by AMPKα1-specific siRNA knockdown. In a monocyte adhesion assay, vaspin reduced TNFα-induced monocyte adhesion in an AMPK-dependent manner. Western blotting (AMPK, ACC phosphorylation); siRNA knockdown of AMPKα1; NF-κB activation assay; adhesion molecule expression; monocyte-endothelial adhesion assay Cardiovascular diabetology Medium 24517399
2017 Vaspin suppresses IL-1β-induced expression and secretion of pro-inflammatory cytokines (IL-6, MCP1, TNFα) in 3T3-L1 adipocytes by inhibiting the NF-κB signaling cascade (IKKα/β, IκB, NF-κB). Endogenous vaspin expression (stable transfection) also positively affected insulin signaling by increasing insulin-stimulated AKT phosphorylation. Stable transfection of 3T3-L1 cells with vaspin; exogenous vaspin treatment; western blotting (IKKα/β, IκB, NF-κB, AKT phosphorylation); cytokine secretion ELISA Molecular and cellular endocrinology Medium 28756250
2016 Central administration of vaspin to the third cerebral ventricle in HFD-fed rats inhibited hepatic glucose production and improved hepatic insulin sensitivity via DVC N-methyl-D-aspartate (NMDA) receptor signaling to the hepatic branch of the vagus nerve. Selective hepatic branch vagotomy or DVC MK-801 (NMDA receptor inhibitor) infusion blocked the central vaspin effect on glucose production and hepatic insulin signaling. Intracerebroventricular infusion; pancreatic euglycemic clamp; hepatic branch vagotomy; DVC MK-801 infusion; western blotting (hepatic insulin signaling: IR, IRS-1, Akt, FOXO1 phosphorylation); hepatic gluconeogenic gene expression International journal of obesity (2005) Medium 26975443
2013 Vaspin inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells and bone marrow cells, and inhibits RANKL-induced expression of NFATc1, matrix metalloproteinase-9, and cathepsin K. RANKL-induced osteoclast differentiation assay (RAW264.7 cells and bone marrow cells); western blotting/PCR for NFATc1, MMP-9, cathepsin K Connective tissue research Medium 23323745
2012 Vaspin inhibits apoptosis in human osteoblasts (hOBs) induced by serum deprivation via activation of the MAPK/ERK signaling pathway, upregulating Bcl-2 and downregulating Bax. The ERK inhibitor PD98059 blocked vaspin-induced ERK phosphorylation. Vaspin did not stimulate phosphorylation of p38, JNK, or Akt. Serum deprivation apoptosis model; ELISA and TUNEL apoptosis assays; western blotting (ERK, p38, JNK, Akt, Bcl-2, Bax); ERK inhibitor PD98059 blockade Amino acids Medium 23135225
2019 Vaspin is secreted from human subcutaneous adipose tissue and skeletal muscle, is more highly expressed in obese older individuals, and activates the PI3K/AKT axis independent of insulin receptor activation, promotes GLUT4 expression and translocation, and sensitizes older obese human skeletal muscle to insulin-mediated glucose uptake. Human tissue expression profiling; recombinant vaspin treatment of human skeletal muscle cells; western blotting (PI3K/AKT); GLUT4 translocation assay; glucose uptake assay The Journal of endocrinology Medium 30721136
2016 Vaspin attenuates high-glucose-induced vascular smooth muscle cell (VSMC) proliferation and chemokinesis by inhibiting ROS generation, NADPH oxidase activity, and the MAPK, PI3K/Akt, and NF-κB signaling pathways, including abolishing phosphorylation of p47phox, Akt, p38, JNK1/2, insulin receptor, IRS-1, IRS-2, and suppressing NF-κB activity and IκBα phosphorylation. EdU cell proliferation assay; scratch migration assay; H2DCFDA ROS assay; NADPH oxidase activity assay; luciferase reporter (NF-κB); western blotting (multiple signaling proteins) Atherosclerosis Medium 23497782
2020 Vaspin expression in porcine ovarian follicle cells is regulated by gonadotropins, insulin, IGF-1, and steroids (progesterone, testosterone, estradiol) through JAK/STAT, ERK1/2, PI3K, and AMPK kinase pathways as well as NF-κB. Vaspin stimulates basal steroidogenesis (progesterone and estradiol) via GRP78 receptor and PKA; the stimulatory effect was reversed by PKA inhibitor KT5720 and GRP78 siRNA knockdown. Real-time PCR and western blot (vaspin, GRP78); PKA inhibitor (KT5720); siRNA knockdown of GRP78; steroid hormone secretion ELISA Biology of reproduction Medium 32149334
2021 Vaspin enhances human granulosa cell steroidogenesis, proliferation, and viability through GRP78 receptor in a concentration-dependent manner, confirmed by GRP78 siRNA knockdown which abrogated vaspin effects. Recombinant vaspin treatment of human granulosa cells; siRNA knockdown of GRP78; steroidogenesis assay; proliferation and viability assays; western blot; RT-qPCR The Journal of endocrinology Medium 33608490
2020 Vaspin promotes osteoblastic differentiation and ALP activity in rat primary osteoblasts via activation of the Smad2/3-Runx2 signaling pathway, upregulating Runx2, Osterix, and Collagen alpha1; in vivo, vaspin administration to HFD rats antagonized bone loss. Primary rat osteoblast differentiation assay; ALP activity assay; western blotting (Smad2/3, p-Smad2/3, Runx2); real-time PCR; micro-CT and three-point bending tests (in vivo) Nutrition & metabolism Medium 31993071
2022 Vaspin reduces hepatocyte steatosis and fibrosis via the GRP78 receptor by activating AMPK, increasing fatty acid oxidation and secretion, decreasing lipogenesis and fatty acid uptake, and reducing α-SMA and TGF-β1 expression in co-cultured hepatocyte/stellate cell model. HepG2/LX-2 co-culture model; Nile Red lipid assay; flow cytometry; RT-qPCR (lipid metabolism genes); western blot (α-SMA, TGF-β1, AMPK); GRP78 receptor blockade Journal of physiology and biochemistry Low 35001345
2009 Vaspin (SERPINA12) was identified from visceral white adipose tissue (WAT) of OLETF rats using PCR-based cDNA subtraction. Administration of recombinant vaspin into high-fat high-sucrose chow-induced obese ICR mice improved glucose tolerance and insulin sensitivity. cDNA subtraction cloning; recombinant protein administration to obese mice; glucose tolerance test; insulin sensitivity assay Expert opinion on investigational drugs Low 18321232
2016 Vaspin is specifically expressed in keratinocytes (KCs) in skin, closely associated with epidermal differentiation. Downregulation of vaspin in KCs in psoriasis resulted in decreased differentiation-associated gene expression and upregulation of inflammation-associated psoriasis signature genes. Vaspin decreased secretion of TNF-α, IL-1β, IL-6, IL-8, and MCP-1 by co-cultured immune cells; application of vaspin inhibited myeloid cell infiltration in a psoriasis-like mouse model. Immunohistochemistry; RT-PCR; siRNA knockdown of vaspin in KCs; co-culture of KCs with immune cells; in vivo mouse psoriasis model with vaspin application The American journal of pathology Medium 26783881
2017 Vaspin in brown adipose tissue (BAT) is specifically induced at mRNA and protein levels by cold exposure and obesogenic (high-fat or high-sugar) diets in mice. Cold-induced BAT vaspin expression is accompanied by acute reduction in DNA methylation within the vaspin promoter in BAT, providing an epigenetic regulatory mechanism. mRNA and protein expression analysis in adipose tissue depots; adipogenesis and adrenergic stimulation experiments in brown adipocytes; vaspin promoter DNA methylation analysis Molecular metabolism Medium 28580279
2019 Vaspin promotes porcine granulosa cell proliferation, cell cycle progression into S and G2/M phases, and decreases apoptosis. GRP78 siRNA silencing and pharmacological inhibitors of MAP3/1 (ERK1/2), STAT3, and AKT blocked vaspin-induced proliferation and enhanced caspase-3/7 activities, establishing GRP78 as the receptor and these kinases as downstream mediators. alamarBlue proliferation assay; flow cytometry (cell cycle); Caspase-Glo 3/7 assay; siRNA silencing of GRP78; pharmacological kinase inhibitors; western blotting (cyclin D, E, A; BAX, BCL2, caspases, p53) International journal of molecular sciences Medium 31752432
2020 Vaspin enhances porcine luteal cell angiogenesis, proliferation, and decreases apoptosis via GRP78 receptor and MAP3/1 kinase pathways; GRP78 siRNA and MAP3/1 inhibitor (PD98059) reversed all vaspin effects. Luteal cell culture; alamarBlue proliferation; Caspase-Glo 3/7; angiogenic factor ELISA and PCR; GRP78 siRNA; PD98059 inhibition; western blotting International journal of molecular sciences Medium 32957618
2020 Vaspin affects luteal cell steroidogenesis (stimulates progesterone synthesis), increases luteotropic PGE2:luteolytic PGF2α ratio, and activates PKA and MAP3/1 kinases via GRP78 receptor, as shown by GRP78 siRNA knockdown and MAP3/1 inhibitor reversal of vaspin effects. Luteal cell culture; GRP78 siRNA knockdown; MAP3/1 inhibitor (PD98059); PKA phosphorylation western blot; steroid hormone ELISA The Journal of endocrinology Medium 33108345
2020 SerpinA12 (vaspin) secreted by hepatic stellate cells (HSCs) is protective against ethanol-induced steatosis in hepatocytes in vitro. In NRP-1 knockdown HSCs, SerpinA12 secretion was increased, and recombinant SerpinA12 was protective against ethanol-induced lipid droplet formation in hepatocytes. SerpinA12 was decreased in serum and liver tissue from patients with alcoholic hepatitis. HSC conditioned medium experiments; adipokine/inflammatory protein array; recombinant protein treatment of hepatocytes in vitro; lipid droplet assay; immunocompetent HCC mouse model Journal of hepatology Medium 32087348
2009 Vaspin protein is expressed in human and rat placenta with tissue-specific localization: in rat, in trophoblast of the fetal labyrinth; in human, in cytotrophoblast and syncytiotrophoblast in first trimester and syncytiotrophoblast in third trimester. Food restriction increases placental vaspin mRNA and protein levels in rats, indicating nutritional regulation of vaspin expression. Immunohistochemistry (human and rat placenta); RT-PCR; food restriction experiment in rats Histology and histopathology Low 19554505
2009 Vaspin (TNF-α-stimulated human umbilical vein endothelial cells): vaspin (10–100 ng/mL, 24 h) had no effect on basal endothelial cell morphology and did not inhibit TNF-α-induced activation of JNK, p38, or NF-κB (with only slight Akt inhibition), and did not decrease TNF-α-induced expression of VCAM-1, ICAM-1, E-selectin, COX-2, MCP-1, tissue factor, or PAI-1. Western blotting (JNK, p38, NF-κB, Akt); mRNA expression; protein expression in HUVECs with TNF-α stimulation The Journal of veterinary medical science Medium 19801900

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 308 17991760
2008 Vaspin: a novel serpin with insulin-sensitizing effects. Expert opinion on investigational drugs 146 18321232
2008 Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance. Diabetes 140 18375437
2011 Vaspin in obesity and diabetes: pathophysiological and clinical significance. Endocrine 124 22139797
2007 Serum levels of the adipokine vaspin in relation to metabolic and renal parameters. The Journal of clinical endocrinology and metabolism 121 17956947
2013 Vaspin inhibits kallikrein 7 by serpin mechanism. Cellular and molecular life sciences : CMLS 120 23370777
2011 Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia 116 21465327
2012 Vaspin is an adipokine ameliorating ER stress in obesity as a ligand for cell-surface GRP78/MTJ-1 complex. Diabetes 113 22837305
2010 Vaspin and visfatin/Nampt are interesting interrelated adipokines playing a role in the pathogenesis of type 2 diabetes mellitus. Metabolism: clinical and experimental 102 20605615
2014 Vaspin (serpinA12) in obesity, insulin resistance, and inflammation. Journal of peptide science : an official publication of the European Peptide Society 89 24596079
2017 Role of Omentin, Vaspin, Cardiotrophin-1, TWEAK and NOV/CCN3 in Obesity and Diabetes Development. International journal of molecular sciences 85 28809783
2011 Potential role of leptin, adiponectin and three novel adipokines--visfatin, chemerin and vaspin--in chronic hepatitis. Molecular medicine (Cambridge, Mass.) 76 21738955
2011 Vaspin protects vascular endothelial cells against free fatty acid-induced apoptosis through a phosphatidylinositol 3-kinase/Akt pathway. Biochemical and biophysical research communications 74 21893030
2013 Vaspin attenuates high glucose-induced vascular smooth muscle cells proliferation and chemokinesis by inhibiting the MAPK, PI3K/Akt, and NF-κB signaling pathways. Atherosclerosis 72 23497782
2008 A novel adipocytokine, visceral adipose tissue-derived serine protease inhibitor (vaspin), and obesity. The Journal of international medical research 72 18652756
2015 The role of vaspin in the development of metabolic and glucose tolerance disorders and atherosclerosis. BioMed research international 68 25945347
2011 Plasma vaspin concentrations are elevated in metabolic syndrome in men and are correlated with coronary atherosclerosis in women. Clinical endocrinology 61 21545478
2010 Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease. Metabolism: clinical and experimental 60 20580037
2010 Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children. International journal of obesity (2005) 59 20856257
2020 Hepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12. Journal of hepatology 58 32087348
2012 Serum vaspin concentrations are closely related to insulin resistance, and rs77060950 at SERPINA12 genetically defines distinct group with higher serum levels in Japanese population. The Journal of clinical endocrinology and metabolism 57 22539588
2017 Vaspin suppresses cytokine-induced inflammation in 3T3-L1 adipocytes via inhibition of NFκB pathway. Molecular and cellular endocrinology 56 28756250
2021 Review: Vaspin (SERPINA12) Expression and Function in Endocrine Cells. Cells 55 34359881
2014 Vaspin inhibits cytokine-induced nuclear factor-kappa B activation and adhesion molecule expression via AMP-activated protein kinase activation in vascular endothelial cells. Cardiovascular diabetology 54 24517399
2012 Vaspin increases nitric oxide bioavailability through the reduction of asymmetric dimethylarginine in vascular endothelial cells. PloS one 50 23284999
2016 Vaspin regulates the osteogenic differentiation of MC3T3-E1 through the PI3K-Akt/miR-34c loop. Scientific reports 48 27156573
2012 Vaspin attenuates the apoptosis of human osteoblasts through ERK signaling pathway. Amino acids 48 23135225
2008 Vaspin (SERPINA12) genotypes and risk of type 2 diabetes: Results from the MONICA/KORA studies. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 46 18726871
2011 Serum visfatin and vaspin levels in prepubertal children: effect of obesity and weight loss after behavior modifications on their secretion and relationship with glucose metabolism. International journal of obesity (2005) 42 21266955
2017 Vaspin protects against LPS‑induced ARDS by inhibiting inflammation, apoptosis and reactive oxygen species generation in pulmonary endothelial cells via the Akt/GSK‑3β pathway. International journal of molecular medicine 41 29039444
2017 Effects of vaspin on pancreatic β cell secretion via PI3K/Akt and NF-κB signaling pathways. PloS one 40 29240812
2019 Molecular Mechanisms of Vaspin Action - From Adipose Tissue to Skin and Bone, from Blood Vessels to the Brain. Advances in experimental medicine and biology 38 30051323
2019 Nesfatin-1 and Vaspin as Potential Novel Biomarkers for the Prediction and Early Diagnosis of Gestational Diabetes Mellitus. International journal of molecular sciences 37 30621139
2009 Vaspin and amylin are expressed in human and rat placenta and regulated by nutritional status. Histology and histopathology 37 19554505
2019 In Vitro Effects of Vaspin on Porcine Granulosa Cell Proliferation, Cell Cycle Progression, and Apoptosis by Activation of GRP78 Receptor and Several Kinase Signaling Pathways Including MAP3/1, AKT, and STAT3. International journal of molecular sciences 35 31752432
2018 Vaspin protects rats against myocardial ischemia/reperfusion injury (MIRI) through the TLR4/NF-κB signaling pathway. European journal of pharmacology 35 30063916
2016 Anti-Inflammatory Action of Keratinocyte-Derived Vaspin: Relevance for the Pathogenesis of Psoriasis. The American journal of pathology 35 26783881
2016 Chemerin, visfatin, and vaspin serum levels in relation to bone mineral density in patients with inflammatory bowel disease. European journal of gastroenterology & hepatology 35 26934527
2019 Vaspin promotes insulin sensitivity in elderly muscle and is upregulated in obesity. The Journal of endocrinology 34 30721136
2017 Brown adipose tissue (BAT) specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation. Molecular metabolism 33 28580279
2013 Vaspin attenuates RANKL-induced osteoclast formation in RAW264.7 cells. Connective tissue research 33 23323745
2012 Vaspin--a link of obesity and psoriasis? Experimental dermatology 33 22417310
2012 Association between chemerin rs17173608 and vaspin rs2236242 gene polymorphisms and the metabolic syndrome, a preliminary report. Gene 33 22982016
2010 Association between serum vaspin concentrations and visceral adipose tissue in Korean subjects. Metabolism: clinical and experimental 33 20060144
2018 Effects of Vaspin on Insulin Resistance in Rats and Underlying Mechanisms. Scientific reports 32 30202052
2010 Omentin-1 and vaspin are present in the fetus and neonate, and perinatal concentrations are similar in normal and growth-restricted pregnancies. Metabolism: clinical and experimental 32 20488498
2009 Serum vaspin level in relation to postprandial plasma glucose concentration in subjects with diabetes. Chinese medical journal 32 19951565
2018 The Association Between Serum Vaspin and Omentin-1 Levels in Obese Children with Metabolic Syndrome. Metabolic syndrome and related disorders 31 29319392
2015 Vaspin promotes 3T3-L1 preadipocyte differentiation. Experimental biology and medicine (Maywood, N.J.) 31 25585626
2015 Vaspin alleviates dysfunction of endothelial progenitor cells induced by high glucose via PI3K/Akt/eNOS pathway. International journal of clinical and experimental pathology 30 25755737
2010 Serum vaspin and C-reactive protein levels in women with polycystic ovaries and polycystic ovary syndrome. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 30 20626239
2011 Vaspin plasma concentrations and mRNA expressions in patients with stable and unstable angina pectoris. Clinical chemistry and laboratory medicine 29 21913793
2020 Loss-of-Function Variants in SERPINA12 Underlie Autosomal Recessive Palmoplantar Keratoderma. The Journal of investigative dermatology 28 32247861
2019 A fluorescent lateral flow biosensor for the quantitative detection of Vaspin using upconverting nanoparticles. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 28 31606675
2018 Biochemical and molecular evidence on the role of vaspin in early detection of the insulin resistance in a rat model of high-fat diet and use of diazinon. Toxicology 28 30359674
2012 Genetic variation in the vaspin gene affects circulating serum vaspin concentrations. International journal of obesity (2005) 28 22907691
2014 Relationship of vaspin and apelin levels with insulin resistance and atherosclerosis in metabolic syndrome. Minerva endocrinologica 27 24736484
2019 Serum Vaspin as a Predictor of Adverse Cardiac Events in Acute Myocardial Infarction. Journal of the American Heart Association 26 30646836
2018 Anti-Atherogenic Effects of Vaspin on Human Aortic Smooth Muscle Cell/Macrophage Responses and Hyperlipidemic Mouse Plaque Phenotype. International journal of molecular sciences 26 29891806
2016 Vaspin, resistin, retinol-binding protein-4, interleukin-1α and interleukin-6 in patients with nonalcoholic fatty liver disease. Annals of hepatology 26 27493109
2020 Role of vaspin in porcine ovary: effect on signaling pathways and steroid synthesis via GRP78 receptor and protein kinase A†. Biology of reproduction 25 32149334
2019 Vaspin in the pig ovarian follicles: expression and regulation by different hormones. Reproduction (Cambridge, England) 25 31063973
2016 Central administration of vaspin inhibits glucose production and augments hepatic insulin signaling in high-fat-diet-fed rat. International journal of obesity (2005) 25 26975443
2016 Assessment of serum chemerin, vaspin and omentin-1 levels in patients with polycystic ovary syndrome. The Journal of international medical research 25 27225862
2015 Mediatory effect of circulating vaspin on resting metabolic rate in obese individuals. European journal of nutrition 25 26058881
2014 Association of vaspin with metabolic syndrome: the pivotal role of insulin resistance. Diabetes & metabolism journal 25 24851208
2013 Vaspin and C-reactive protein levels in hyperemesis gravidarum. European review for medical and pharmacological sciences 25 23329536
2011 Circulating levels of the adipokines vaspin and omentin in patients with juvenile idiopathic arthritis, and relation to disease activity. Clinical and experimental rheumatology 25 22032341
2023 SERPINA12 promotes the tumorigenic capacity of HCC stem cells through hyperactivation of AKT/β-catenin signaling. Hepatology (Baltimore, Md.) 24 36630996
2020 Vaspin antagonizes high fat-induced bone loss in rats and promotes osteoblastic differentiation in primary rat osteoblasts through Smad-Runx2 signaling pathway. Nutrition & metabolism 24 31993071
2019 The role of the adipocytokines vaspin and visfatin in vascular endothelial function and insulin resistance in obese children. BMC endocrine disorders 23 31771561
2016 Association between vaspin level and coronary artery disease in patients with type 2 diabetes. Diabetes research and clinical practice 23 26972957
2015 Association of chemerin Rs17173608 and vaspin Rs2236242 gene polymorphisms with metabolic syndrome in Egyptian women. Endocrine research 23 26472663
2015 Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals. PloS one 23 26670468
2015 Vaspin attenuates the progression of atherosclerosis by inhibiting ER stress-induced macrophage apoptosis in apoE‑/‑ mice. Molecular medicine reports 22 26708512
2013 Associations between tissue visfatin/nicotinamide, phosphoribosyltransferase (Nampt), retinol binding protein-4, and vaspin concentrations and insulin resistance in morbidly obese subjects. Mediators of inflammation 22 24367155
2020 Flutamide Alters the Expression of Chemerin, Apelin, and Vaspin and Their Respective Receptors in the Testes of Adult Rats. International journal of molecular sciences 21 32580404
2015 Relationship of plasma level of chemerin and vaspin to early atherosclerotic changes and cardiac autonomic neuropathy in adolescent type 1 diabetic patients. Journal of pediatric endocrinology & metabolism : JPEM 21 25210758
2012 Vaspin gene in rat adipose tissue: relation to obesity-induced insulin resistance. Molecular and cellular biochemistry 20 23135683
2009 Vaspin can not inhibit TNF-alpha-induced inflammation of human umbilical vein endothelial cells. The Journal of veterinary medical science 20 19801900
2021 Vaspin, a novel adipokine in woman granulosa cells physiology and PCOS pathogenesis? The Journal of endocrinology 19 33608490
2020 Novel Insights on the Corpus Luteum Function: Role of Vaspin on Porcine Luteal Cell Angiogenesis, Proliferation and Apoptosis by Activation of GRP78 Receptor and MAP3/1 Kinase Pathways. International journal of molecular sciences 19 32957618
2020 VASPIN reduces inflammation and endoplasmic reticulum stress of renal tubular epithelial cells by inhibiting HMGB1 and relieves renal ischemia-reperfusion injury. European review for medical and pharmacological sciences 19 32964986
2021 A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease. Communications biology 18 33742129
2020 The role of vaspin in porcine corpus luteum. The Journal of endocrinology 18 33108345
2017 Obesity risk prediction among women of Upper Egypt: The impact of serum vaspin and vaspin rs2236242 gene polymorphism. Gene 18 28479386
2014 Expression of vaspin in the joint and the levels in the serum and synovial fluid of patients with osteoarthritis. International journal of clinical and experimental medicine 18 25419381
2012 Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL. Journal of lipid research 18 23160181
2018 Vaspin Prevents Tumor Necrosis Factor-α-Induced Apoptosis in Cardiomyocytes by Promoting Autophagy. Journal of cardiovascular pharmacology 17 29734265
2016 The association of vaspin rs2236242 and leptin rs7799039 polymorphism with metabolic syndrome in Egyptian women. Turkish journal of medical sciences 17 27966294
2015 Plasma levels and placental expression of vaspin in pregnant women with diabetes mellitus. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 17 25608237
2015 Resveratrol attenuates visfatin and vaspin genes expression in adipose tissue of rats with type 2 diabetes. Iranian journal of basic medical sciences 17 26221476
2014 Association between vaspin rs2236242 gene polymorphism and polycystic ovary syndrome risk. Gene 17 24530312
2010 Calorie control increased vaspin levels of serum and periepididymal adipose tissue in diet-induced obese rats in association with serum free fatty acid and tumor necrosis factor alpha. Chinese medical journal 16 20497691
2022 Vaspin attenuates steatosis-induced fibrosis via GRP78 receptor by targeting AMPK signaling pathway. Journal of physiology and biochemistry 15 35001345
2020 Expression and Impact of Vaspin on In Vitro Oocyte Maturation through MAP3/1 and PRKAA1 Signalling Pathways. International journal of molecular sciences 15 33302416
2015 Changes and clinical significance of serum vaspin levels in patients with type 2 diabetes. Genetics and molecular research : GMR 15 26436376
2022 New insights into cell apoptosis and proliferation: the potential role of vaspin. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 14 35377336
2015 Medullary Thyroid Carcinoma--Circulating Status of Vaspin and Retinol Binding Protein-4 in Iranian Patients. Asian Pacific journal of cancer prevention : APJCP 14 26434866
2014 Serum vaspin levels and vaspin mRNA expression in subcutaneous adipose tissue in women with gestational diabetes mellitus. European journal of obstetrics, gynecology, and reproductive biology 14 25277770

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