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serpin family A member 12 OKDB#: 4981
 Symbols: SERPINA12 Species: human
 Synonyms: OL-64  Locus: 14q32.13 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment
General function Ligand, Hormone, Extracellular binding protein, Anti-apoptotic
Comment
Cellular localization Secreted
Comment candidate123//// Circulating vaspin levels and nutritional status and insulin resistance in polycystic ovary syndrome. Franik G et al. (2020) The study aimed to assess the associations between circulating vaspin levels and nutritional status (assessed on tha basis of BMI) as well as insulin resistance in PCOS. Eighty-seven PCOS women, 48 obese and 39 normal weight, were enrolled in the cross-sectional study. Seventy-two Non-PCOS women, 41 obese and 31 normal weight, constituted a control group. Body mass, height and waist circumference as well as body composition by bioimpedance were measured. In the morning (16h after the last meal) we determined: serum glucose, insulin, androgens, gonadotropin (LH, FSH) and sex hormone-binding globulin (SHBG) as well as plasma vaspin levels. Standard HOMA-IR formula was used to assess insulin resistance (IR). Plasma vaspin levels were significantly lower in PCOS, both normal weight and obese, than in Non-PCOS groups. Vaspin levels were similar in normal weight and obese PCOS subgroups. There was no association between plasma vaspin levels and anthropometric parameters in PCOS group. While in Non-PCOS group a negative correlation between plasma vaspin levels and body mass (r = -0.26; p < 0.05) was found. We did not observe correlations between plasma vaspin levels and serum glucose and insulin concentrations as well as HOMA-IR values, however, in multivariable, stepwise backward regression waist circumference and HOMA-IR values explained 18.0% of plasma vaspin levels variability in the study subjects. PCOS occurrence is associated with decreased vaspin levels. The influence of nutritional status on vaspin level observed in Non-PCOS is abolished in PCOS women, possibly by more severe insulin resistance.//////////////////
Ovarian function Antral follicle growth, Steroid metabolism
Comment Comparison of Serum Adiponectin and Osteopontin Levels along with Metabolic Risk Factors Between Obese and Lean women with and without PCOS. Alatas SE et al. (2020) To investigate the possible relation between serum adiponectin and osteopontin levels as metabolic risk markers among women with different PCOS phenotypes Material and Methods: In an University Hospital setting PCOS patients diagnosed according to Rotterdam Consensus Conference criteria, excluded of other endocrinopathies, and having spontaneous menarche and normal sexual development, and with BMI between 18 and 35 were recruited. Overall, 57 PCOS patients and age and BMI matched 57 healthy controls were included to the study. LF/FSH ration, FAI, and DHEAS-S was found to be significantly higher in women with PCOS. There was significant interaction between PCOS status and obesity for serum adiponectin levels. Although mean adiponectin and osteopontin levels were similar among cases and controls, a further two-way ANOVA comparison within lean and obese subgroups revealed adiponectin to be significantly lower in lean PCOS women than lean controls. LH/FSH ratio and adiponectin levels were all found to differ between lean counterparts, however they did not show any corelation with metabolic markers (cholesterol panel, HOMA or CRP levels) neither in overall lean women nor in lean PCOS subgroup. Serum adiponectin levels in lean PCOS women are significantly lower than that of in lean controls. On the other hand mean adiponectin and osteopontin levels were similar between PCOS cases and controls overall. There is a need for prospective data regarding the clinical value of adiponectin investigating it as a long-term metabolic risk factor in lean cases.////////////////// Role of vaspin in porcine ovary: effect on signaling pathways and steroid synthesis via GRP78 receptor and protein kinase A. Kurowska P et al. (2020) Vaspin, visceral adipose tissue-derived serine protease inhibitor, is involved in the development of obesity, insulin resistance, inflammation and energy metabolism. Our previous study showed vaspin expression and its regulation in the ovary; however, the role of this adipokine in ovarian cells has never been studied. Here, we studied in vitro the effect of vaspin on various kinase signaling pathways: mitogen-activated kinase (MAP3/1), serine/threonine kinase (AKT), signal transducer and activator of transcription 3 (STAT3) protein kinase AMP (PRKAA1), protein kinase A (PKA) and on expression of nuclear factor kappa B (NFKB2) as well as on steroid synthesis by porcine ovarian cells. By Western blot, we found that vaspin (1 ng/ml), in a time-dependent manner, increased phosphorylation of MAP3/1, AKT, STAT3, PRKAA1 and PKA, while it decreased expression of NFKB2. We observed that vaspin, in a dose-dependent manner, increased basal steroid hormones secretion (progesterone and estradiol), mRNA and protein expression of steroid enzymes using real-time PCR and Western blot, respectively, and the mRNA of gonadotropins (FSHR, LHCGR) and steroids (PGR, ESR2) receptors. The stimulatory effect of vaspin on basal steroidogenesis was reversed when ovarian cells were cultured in the presence of a PKA pharmacological inhibitor (KT5720) and when GRP78 receptor was knocked down (siRNA). However, in the presence of insulin-like growth factor type 1 and gonadotropins, vaspin reduced steroidogenesis. Thus, vaspin, by activation of various signaling pathways and stimulation of basal steroid production via GRP78 receptor and PKA, could be a new regulator of porcine ovarian function.////////////////// 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. Kurowska P et al. (2019) Vaspin, a visceral adipose tissue-derived serine protease inhibitor, is expressed in the porcine ovary; it induces the activation of various kinases and steroidogenesis. The aim of this study was to examine the effect of vaspin on granulosa (Gc) proliferation, cell cycle regulation, and apoptosis. Porcine Gc was incubated with vaspin (0.01-10 ng/mL) for 24 to 72 h, proliferation was measured using alamarBlue assay, cell cycle progression was assessed using flow cytometry, and cyclin (D, E, and A) protein expression was measured using immunoblotting. Apoptosis was assessed by measuring caspase activity using Caspase-glo 3/7 assay. Furthermore, histone-associated DNA fragments levels were measured using a cell-death detection ELISA; BAX (bcl-2-like protein 4), BCL2 (B-cell lymphoma 2), caspases (-3, -8, and -9), p53 mRNA, and protein expression were assessed using real time PCR and immunoblotting. We found that vaspin significantly enhanced Gc proliferation and cell cycle progression into the S and G2/M phases and decreased apoptosis. We observed that siRNA silencing of the glucose-regulated protein (GRP78) receptor and pharmacological inhibitors of mitogen-activated kinase (MAP3/1/ERK1/2), Janus kinase (STAT3) and protein kinase B (AKT) blocked the ability of vaspin cell proliferation and enhanced caspase-3/7 activities. These results suggest that vaspin via mitogenic effect on porcine Gc acts as a new regulator of ovarian growth, development, or folliculogenesis.//////////////////
Expression regulated by FSH, LH
Comment Vaspin in the pig ovarian follicles: expression and regulation by different hormones. Kurowska P et al. (2019) Vaspin, also known as visceral adipose tissue-derived serine protease inhibitor, is a member of the serine protease inhibitor family. Its expression is associated with obesity, insulin resistance and type 2 diabetes, and elevated concentration is observed in polycystic ovary syndrome. However, vaspin has never been studied in the ovary. Here, we identified vaspin in two prolific breeds of pigs: fat Meishan (MS) and lean Large White (LW). We then investigated the molecular mechanism involved in the regulation of its expression in response to gonadotropins, insulin, insulin-like growth factor type 1 (IGF-1) and steroids (progesterone, testosterone and estradiol) in ovarian follicles cells. Using real-time PCR and Western blot, we found higher vaspin mRNA and protein expression in the ovarian follicles and adipose tissue at 10-12 days of the oestrous cycle in MS compared to LW. Moreover, vaspin expression, as well as its concentration in plasma and follicular fluid, decreased in ovarian follicles of LW during days of the oestrous cycle, while the opposite results were noted in MS. Immunohistochemistry showed vaspin in granulosa, theca, cumulus cells and oocytes as well as in adipocytes. Vaspin level in the ovary increased by gonadotropin, insulin, IGF-1 and steroids stimulation through kinases JAK/Stat, ERK1/2, PI3K and AMPK, as well as factor NF-κB. These findings all show vaspin expression and regulation in the pig ovary, indicating vaspin as a new regulator in female reproduction. Future studies will be necessary for understanding role of vaspin on ovarian physiology providing new insights into the pathology of ovaries.//////////////////
Ovarian localization Oocyte, Cumulus, Granulosa, Theca
Comment
Follicle stages
Comment
Phenotypes PCO (polycystic ovarian syndrome)
Mutations 1 mutations

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Association between vaspin rs2236242 gene polymorphism and polycystic ovary syndrome risk. Kohan L 2014 et al. Vaspin, an adipocytokine that has been isolated from the visceral adipose tissue, is a member of the serine protease inhibitor family. In humans, serum vaspin levels are correlated with body mass index (BMI) and obese women with polycystic ovary syndrome (PCOS). The present study is the first investigation to examine the association between vaspin rs2236242 gene polymorphism and risk of PCOS in Iranian patients. This case-control study was performed on 150 patients with PCOS and 150 healthy women. The vaspin genotypes were determined using tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). Our finding showed that there are significant differences in genotype frequencies between case and control group regarding vaspin rs2236242 polymorphism (OR=0.59, CI=0.37-0.95, p=0.03). The A allele decreased the risk of PCOS (OR=0.67, CI=0.46-0.96, p=0.03) as compared to the T allele. There was no significant association between vaspin rs2236242 gene polymorphism and PCOS after adjusting genotypes for BMI. In conclusion, our data suggest a significant association between vaspin rs2236242 polymorphism and the PCOS but this relationship is affected by obesity status. /////////////////////////

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created: Feb. 19, 2014, 9:58 a.m. by: hsueh   email:
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last update: Nov. 3, 2020, 11:22 p.m. by: hsueh    email:



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